Does RNA serve as the genetic material of some plants and animals along with viruses?

My teacher mentioned that some plants and animals have RNA as genetic material but did not substantiate his statement with examples. I'm wondering if it is so? I have searched the internet but have found no such information.

There are no animals or plants with RNA genomes. There was a mistaken belief in the 1920s that plant genetic material was RNA whereas animals had DNA, but this was finally disproved by JN Davidson in the 1940s.

Why some viruses have DNA and some have RNA?

All viruses have genetic material (a genome) made of nucleic acid. You, like all other cell-based life, use DNA as your genetic material. Viruses, on the other hand, may use either RNA or DNA, both of which are types of nucleic acid.

Beside above, do bacteria have DNA or RNA? Solution: Bacteria have both DNA and RNA as their genetic material. The DNA in bacteria, just like eukaryotes is stored in form of a chromosomal structure along with associated proteins and RNA, but as a circular double-stranded structure, unlike the other organisms.

Likewise, people ask, what type of virus uses RNA and not DNA?

Some examples of retroviruses are hepatitis viruses and HIV. When these viruses enter a host cell, they must first convert their RNA into DNA. This process, called reverse transcription, enables the virus to inject its genetic material into the host cell and use the host's biochemical machinery, similar to a DNA virus.

How do viruses use RNA as genetic material?

Virus-Packing RNA When a virus hijacks a cell, it forces the cell to produce copies of the virus. This process includes creating capsids&mdashthe outer protein shell of a virus. The genetic information of some viruses is so long and complex that it has to be folded and packed tightly to fit inside the capsid.


Genetically modified viruses are generated through genetic modification, which involves the directed insertion, deletion, artificial synthesis, or change of nucleotide sequences in viral genomes using biotechnological methods. While most dsDNA viruses have single monopartite genomes, many RNA viruses have multipartite genomes, it is not necessary for all parts of a viral genome to be genetically modified for the virus to be considered a genetically modified virus. Infectious viruses capable of infection that are generated through artificial gene synthesis of all, or part of their genomes (for example based on inferred historical sequences) may also be considered as genetically modified viruses. Viruses that are changed solely through the action of spontaneous mutations, recombination or reassortment events (even in experimental settings), are not generally considered to be genetically modified viruses.

Viruses are generally modified so they can be used as vectors for inserting new genetic information into a host organism or altering its preexisting genetic material. This can be achieved in at least three processes :

  1. Integration of all, or parts, of a viral genome into the host's genome (e.g. into its chromosomes). When the whole genetically modified viral genome is integrated it is then referred to as a genetically modified provirus. Where DNA or RNA which that has been packaged as part of a virus particle, but may not necessarily contain any viral genes, becomes integrated into a hosts genome this process is known as transduction.
  2. Maintenance of the viral genome within host cells but not as an integrated part of the host's genome.
  3. Where genes necessary for genome editing have been placed into the viral genome using biotechnology methods, [1] editing of the host's genome is possible. This process does not require the integration of viral genomes into the host's genome.

None of these three processes are mutually exclusive. Where only process 2. occurs and it results in the expression of a genetically modified gene this will often be referred to as a transient expression approach.

The capacity to infect host cells or tissues is a necessary requirement for all applied uses of genetically modified viruses. However, a capacity for viral transmission (the transfer of infections between host individuals), is either not required or is considered undesirable for most applications. Only in a small minority of proposed uses is viral transmission considered necessary or desirable, an example is transmissible vaccines. [2] [3] This is because transmissibility considerably complicates to efforts monitor, control, or contain the spread of viruses. [4]

In 1972, the earliest report of the insertion of a foreign sequence into a viral genome was published, when Paul Berg used the EcoRI restriction enzyme and DNA ligases to create the first ever recombinant DNA molecules. [5] This was achieved by joining DNA from the monkey SV40 virus with that of the lambda virus. However, it was not established that either of the two viruses were capable of infection or replication.

In 1974, the first report of a genetically modified virus that could also replicate and infect was submitted for publication by Noreen Murray and Kenneth Murray. [6] Just two months later in August 1974, Marjorie Thomas, John Cameron and Ronald W. Davis submitted a report for publication of a similar achievement. [7]

Collectively, these experiments represented the very start of the development of what would eventually become known as biotechnology or recombinant DNA methods.

Gene therapy Edit

Gene therapy [8] uses genetically modified viruses to deliver genes that can cure diseases in human cells.These viruses can deliver DNA or RNA genetic material to the targeted cells. Gene therapy is also used by inactivating mutated genes that are causing the disease using viruses. [9]

Viruses that have been used for gene therapy are, adenovirus, lentivirus, retrovirus and the herpes simplex virus. [10] The most common virus used for gene delivery come from adenoviruses as they can carry up to 7.5 kb of foreign DNA and infect a relatively broad range of host cells, although they have been known to elicit immune responses in the host and only provide short term expression. Other common vectors are adeno-associated viruses, which have lower toxicity and longer term expression, but can only carry about 4kb of DNA. [11] Herpes simplex viruses is a promising vector, have a carrying capacity of over 30kb and provide long term expression, although it is less efficient at gene delivery than other vectors. [12] The best vectors for long term integration of the gene into the host genome are retroviruses, but their propensity for random integration is problematic. Lentiviruses are a part of the same family as retroviruses with the advantage of infecting both dividing and non-dividing cells, whereas retroviruses only target dividing cells. Other viruses that have been used as vectors include alphaviruses, flaviviruses, measles viruses, rhabdoviruses, Newcastle disease virus, poxviruses, and picornaviruses. [11]

Although primarily still at trial stages, [13] it has had some successes. It has been used to treat inherited genetic disorders such as severe combined immunodeficiency [14] rising from adenosine deaminase deficiency (ADA-SCID), [15] although the development of leukemia in some ADA-SCID patients [11] along with the death of Jesse Gelsinger in another trial set back the development of this approach for many years. [16] In 2009 another breakthrough was achieved when an eight year old boy with Leber’s congenital amaurosis regained normal eyesight [16] and in 2016 GlaxoSmithKline gained approval to commercialise a gene therapy treatment for ADA-SCID. [17] As of 2018, there are a substantial number of clinical trials underway, including treatments for hemophilia, glioblastoma, chronic granulomatous disease, cystic fibrosis and various cancers. [11] Although some successes, gene therapy is still considered a risky technique and studies are still undergoing to ensure safety and effectiveness. [9]

Cancer treatment Edit

Another potential use of genetically modified viruses is to alter them so they can directly treat diseases. This can be through expression of protective proteins or by directly targeting infected cells. In 2004, researchers reported that a genetically modified virus that exploits the selfish behaviour of cancer cells might offer an alternative way of killing tumours. [18] [19] Since then, several researchers have developed genetically modified oncolytic viruses that show promise as treatments for various types of cancer. [20] [21] [22] [23] [24]

Vaccines Edit

Most vaccines consist of viruses that have been attenuated, disabled, weakened or killed in some way so that their virulent properties are no longer effective. Genetic engineering could theoretically be used to create viruses with the virulent genes removed. In 2001, it was reported that genetically modified viruses can possibly be used to develop vaccines [25] against diseases such as, AIDS, herpes, dengue fever and viral hepatitis by using a proven safe vaccine virus, such as adenovirus, and modify its genome to have genes that code for immunogenic proteins that can spike the immune systems response to then be able to fight the virus. Genetic engineered viruses should not have reduced infectivity, invoke a natural immune response and there is no chance that they will regain their virulence function, which can occur with some other vaccines. As such they are generally considered safer and more efficient than conventional vaccines, although concerns remain over non-target infection, potential side effects and horizontal gene transfer to other viruses. [26] Another approach is to use vectors to create novel vaccines for diseases that have no vaccines available or the vaccines that are do not work effectively, such as AIDS, malaria, and tuberculosis. Vector-based vaccines have already been approved and many more are being developed. [27]

Heart pacemaker Edit

In 2012, US researchers reported that they injected a genetically modified virus into the heart of pigs. This virus inserted into the heart muscles a gene called Tbx18 which enabled heartbeats. The researchers forecast that one day this technique could be used to restore the heartbeat in humans who would otherwise need electronic pacemakers. [28] [29]

Animals Edit

In Spain and Portugal, by 2005 rabbits had declined by as much as 95% over 50 years due diseases such as myxomatosis, rabbit haemorrhagic disease and other causes. This in turn caused declines in predators like the Iberian lynx, a critically endangered species. [30] [31] In 2000 Spanish researchers investigated a genetically modified virus which might have protected rabbits in the wild against myxomatosis and rabbit haemorrhagic disease. [32] However, there was concern that such a virus might make its way into wild populations in areas such as Australia and create a population boom. [30] [33] Rabbits in Australia are considered to be such a pest that land owners are legally obliged to control them. [34]

Genetically modified viruses that make the target animals infertile through immunocontraception have been created [35] as well as others that target the developmental stage of the animal. [36] There are concerns over virus containment [35] and cross species infection. [37]

Trees Edit

Since 2009 genetically modified viruses expressing spinach defensin proteins have been field trialed in Florida (USA). [38] The virus infection of orange trees aims to combat citrus greening disease, that had reduced orange production in Florida 70% since 2005. [39] A permit application has been pending since February 13th 2017 (USDA 17-044-101r) to extend the experimental use permit to an area of 513,500 acres, this would make it the largest permit of this kind ever issued by the USDA Biotechnology Regulatory Services.

Insect Allies program Edit

In 2016 DARPA, an agency of the U.S. Department of Defense, announced a tender for contracts to develop genetically modified plant viruses for an approach involving their dispersion into the environment using insects. [40] [41] The work plan stated:

“Plant viruses hold significant promise as carriers of gene editing circuitry and are a natural partner for an insect-transmitted delivery platform.” [40]

The motivation provided for the program is to ensure food stability by protecting agricultural food supply and commodity crops:

"By leveraging the natural ability of insect vectors to deliver viruses with high host plant specificity, and combining this capability with advances in gene editing, rapid enhancement of mature plants in the field can be achieved over large areas and without the need for industrial infrastructure.” [40]

Despite its name, the “Insect Allies” program is to a large extent a viral program, developing viruses that would essentially perform gene editing of crops in already-planted fields. [42] [43] [44] [45] The genetically modified viruses described in the work plan and other public documents are of a class of genetically modified viruses subsequently termed HEGAAs (horizontal environmental gene alteration agents). The Insect Allies program is scheduled to run from 2017 to 2021 with contracts being executed by three consortia. There are no plans to release the genetically modified viruses into the environment, with testing of the full insect dispersed system occurring in greenhouses (Biosafety level 3 facilities have been mentioned). [46]

Concerns have been expressed about how this program and any data it generates will impact biological weapon control and agricultural coexistence, [47] [48] [49] though there has also been support for its stated objectives. [50]

Lithium-ion batteries Edit

In 2009, MIT scientists created a genetically modified virus has been used to construct a more environmentally friendly lithium-ion battery. [51] [52] [53] The battery was constructed by genetically engineering different viruses such as, the E4 bacteriophage and the M13 bacteriophage, to be used as a cathode. This was done by editing the genes of the virus that code for the protein coat. The protein coat is edited to coat itself in iron phosphate to be able to adhere to highly conductive carbon-nanotubes. The viruses that have been modified to have a multifunctional protein coat can be used as a nano-structured cathode with causes ionic interactions with cations. Allowing the virus to be used as a small battery. Angela Blecher, the scientist who led the MIT research team on the project, says that the battery is powerful enough to be used as a rechargeable battery, power hybrid electric cars, and a number of personal electronics. [54] While both the E4 and M13 viruses can infect and replicate within their bacterial host, it unclear if they retain this capacity after being part of a battery.

Bio-hazard research limitations Edit

The National Institute of Health declared a research funding moratorium on select Gain-of-Function virus research in January 2015. [55] [56] In January 2017, the U.S. Government released final policy guidance for the review and oversight of research anticipated to create, transfer, or use enhanced potential pandemic pathogens (PPP). [57] Questions about a potential escape of a modified virus from a biosafety lab and the utility of dual-use-technology, dual use research of concern (DURC), prompted the NIH funding policy revision. [58] [59] [60]

GMO lentivirus incident Edit

A scientist claims she was infected by a genetically modified virus while working for Pfizer. In her federal lawsuit she says she has been intermittently paralyzed by the Pfizer-designed virus. "McClain, of Deep River, suspects she was inadvertently exposed, through work by a former Pfizer colleague in 2002 or 2003, to an engineered form of the lentivirus, a virus similar to the one that can lead to acquired immune deficiency syndrome, or AIDS." [61] The court found that McClain failed to demonstrate that her illness was caused by exposure to the lentivirus, [62] but also that Pfizer violated whistleblower protection laws. [63]

What are RNA Viruses?

RNA viruses are viruses with RNA in their genomes. These viruses can be further classified as single-stranded RNA viruses and double-stranded RNA viruses. However, most RNA viruses are single-stranded and they can be further classified into negative-sense and positive-sense RNA viruses. Positive-sense RNA serves directly as mRNA. But in order to serve as mRNA, negative-sense RNA must use an RNA polymerase to synthesize a complementary, positive strand.

Figure 02: RNA virus – SARS

RNA viruses belong to group III, IV, and V of the Baltimore classification. Group III includes double-stranded RNA viruses while group IV includes positive-sense single-stranded RNA viruses. Finally, group V includes negative-sense ssRNA viruses. In addition, retroviruses also have a single-stranded RNA genome, but they transcribe via an intermediate of DNA. Hence, they are not considered as RNA viruses. Rhabdovirus, coronavirus, SARS, poliovirus, rhinovirus, hepatitis A virus, and influenza virus, etc., are some examples of RNA viruses.


Viral based vectors emerged in the 1980s as a tool for transgene expression. In 1983, Albert Siegel described the use of viral vectors in plant transgene expression although viral manipulation via cDNA cloning was not yet available. [7] The first virus to be used as a vaccine vector was the vaccinia virus in 1984 as a way to protect chimpanzees against hepatitis B. [8] Non-viral gene delivery was first reported on in 1943 by Avery et al. who showed cellular phenotype change via exogenous DNA exposure. [9]

There are a variety of methods available to deliver genes to host cells. When genes are delivered to bacteria or plants the process is called transformation and when it is used to deliver genes to animals it is called transfection. This is because transformation has a different meaning in relation to animals, indicating progression to a cancerous state. [10] For some bacteria no external methods are need to introduce genes as they are naturally able to take up foreign DNA. [11] Most cells require some sort of intervention to make the cell membrane permeable to DNA and allow the DNA to be stably inserted into the hosts genome.

Chemical Edit

Chemical based methods of gene delivery can use natural or synthetic compounds to form particles that facilitate the transfer of genes into cells. [2] These synthetic vectors have the ability to electrostatically bind DNA or RNA and compact the genetic information to accommodate larger genetic transfers. [5] Chemical vectors usually enter cells by endocytosis and can protect genetic material from degradation. [6]

Heat shock Edit

One of the simplest method involves altering the environment of the cell and then stressing it by giving it a heat shock. Typically the cells are incubated in a solution containing divalent cations (often calcium chloride) under cold conditions, before being exposed to a heat pulse. Calcium chloride partially disrupts the cell membrane, which allows the recombinant DNA to enter the host cell. It is suggested that exposing the cells to divalent cations in cold condition may change or weaken the cell surface structure, making it more permeable to DNA. The heat-pulse is thought to create a thermal imbalance across the cell membrane, which forces the DNA to enter the cells through either cell pores or the damaged cell wall.

Calcium phosphate Edit

Another simple methods involves using calcium phosphate to bind the DNA and then exposing it to cultured cells. The solution, along with the DNA, is encapsulated by the cells and a small amount of DNA can be integrated into the genome. [12]

Liposomes and polymers Edit

Liposomes and polymers can be used as vectors to deliver DNA into cells. Positively charged liposomes bind with the negatively charged DNA, while polymers can be designed that interact with DNA. [2] They form lipoplexes and polyplexes respectively, which are then up-taken by the cells. [13] The two systems can also be combined. [6] Polymer-based non-viral vectors uses polymers to interact with DNA and form polyplexes. [6]

Nanoparticles Edit

The use of engineered inorganic and organic nanoparticles is another non-viral approach for gene delivery. [14] [15]

Physical Edit

Artificial gene delivery can be mediated by physical methods which uses force to introduce genetic material through the cell membrane. [2]

Electroporation Edit

Electroporation is a method of promoting competence. Cells are briefly shocked with an electric field of 10-20 kV/cm, which is thought to create holes in the cell membrane through which the plasmid DNA may enter. After the electric shock, the holes are rapidly closed by the cell's membrane-repair mechanisms.

Biolistics Edit

Another method used to transform plant cells is biolistics, where particles of gold or tungsten are coated with DNA and then shot into young plant cells or plant embryos. [16] Some genetic material enters the cells and transforms them. This method can be used on plants that are not susceptible to Agrobacterium infection and also allows transformation of plant plastids. Plants cells can also be transformed using electroporation, which uses an electric shock to make the cell membrane permeable to plasmid DNA. Due to the damage caused to the cells and DNA the transformation efficiency of biolistics and electroporation is lower than agrobacterial transformation. [17]

Microinjection Edit

Microinjection is where DNA is injected through the cell's nuclear envelope directly into the nucleus. [11]

Sonoporation Edit

Sonoporation uses sound waves create pores in a cell membrane to allow entry of genetic material.

Photoporation Edit

Photoporation is when laser pulses are used to create pores in a cell membrane to allow entry of genetic material.

Magnetofection Edit

Magnetofection uses magnetic particles complexed with DNA and an external magnetic field concentrate nucleic acid particles into target cells.

Hydroporation Edit

A hydrodynamic capillary effect can be used to manipulate cell permeability.

Agrobacterium Edit

In plants the DNA is often inserted using Agrobacterium-mediated recombination, [18] taking advantage of the Agrobacteriums T-DNA sequence that allows natural insertion of genetic material into plant cells. [19] Plant tissue are cut into small pieces and soaked in a fluid containing suspended Agrobacterium. The bacteria will attach to many of the plant cells exposed by the cuts. The bacteria uses conjugation to transfer a DNA segment called T-DNA from its plasmid into the plant. The transferred DNA is piloted to the plant cell nucleus and integrated into the host plants genomic DNA.The plasmid T-DNA is integrated semi-randomly into the genome of the host cell. [20]

By modifying the plasmid to express the gene of interest, researchers can insert their chosen gene stably into the plants genome. The only essential parts of the T-DNA are its two small (25 base pair) border repeats, at least one of which is needed for plant transformation. [21] [22] The genes to be introduced into the plant are cloned into a plant transformation vector that contains the T-DNA region of the plasmid. An alternative method is agroinfiltration. [23] [24]

Viral delivery Edit

Virus mediated gene delivery utilizes the ability of a virus to inject its DNA inside a host cell and takes advantage of the virus' own ability to replicate and implement their own genetic material. Viral methods of gene delivery are more likely to induce an immune response, but they have high efficiency. [6] Transduction is the process that describes virus-mediated insertion of DNA into the host cell. Viruses are a particularly effective form of gene delivery because the structure of the virus prevents degradation via lysosomes of the DNA it is delivering to the nucleus of the host cell. [25] In gene therapy a gene that is intended for delivery is packaged into a replication-deficient viral particle to form a viral vector. [26] Viruses used for gene therapy to date include retrovirus, adenovirus, adeno-associated virus and herpes simplex virus. However, there are drawbacks to using viruses to deliver genes into cells. Viruses can only deliver very small pieces of DNA into the cells, it is labor-intensive and there are risks of random insertion sites, cytopathic effects and mutagenesis. [27]

Viral vector based gene delivery uses a viral vector to deliver genetic material to the host cell. This is done by using a virus that contains the desired gene and removing the part of the viruses genome that is infectious. [2] Viruses are efficient at delivering genetic material to the host cell's nucleus, which is vital for replication. [2]

RNA-based viral vectors Edit

RNA-based viruses were developed because of the ability to transcribe directly from infectious RNA transcripts. RNA vectors are quickly expressed and expressed in the targeted form since no processing is required. Gene integration leads to long-term transgene expression but RNA-based delivery is usually transient and not permanent. [2] Retroviral vectors include oncoretroviral, lentiviral and human foamy virus. [2]

DNA-based viral vectors Edit

DNA-based viral vectors are usually longer lasting with the possibility of integrating into the genome. DNA-based viral vectors include Adenoviridae, adeno-associated virus and herpes simplex virus. [2]

Gene therapy Edit

Several of the methods used to facilitate gene delivery have applications for therapeutic purposes. Gene therapy utilizes gene delivery to deliver genetic material with the goal of treating a disease or condition in the cell. Gene delivery in therapeutic settings utilizes non-immunogenic vectors capable of cell specificity that can deliver an adequate amount of transgene expression to cause the desired effect. [3]

Advances in genomics have enabled a variety of new methods and gene targets to be identified for possible applications. DNA microarrays used in a variety of next-gen sequencing can identify thousands of genes simultaneously, with analytical software looking at gene expression patterns, and orthologous genes in model species to identify function. [28] This has allowed a variety of possible vectors to be identified for use in gene therapy. As a method for creating a new class of vaccine, gene delivery has been utilized to generate a hybrid biosynthetic vector to deliver a possible vaccine. This vector overcomes traditional barriers to gene delivery by combining E. coli with a synthetic polymer to create a vector that maintains plasmid DNA while having an increased ability to avoid degradation by target cell lysosomes. [29]

Modern Concept of Gene (With Diagram)

In this article we will discuss about Modern Concept of Gene:- 1. Introduction to the Modern Concept of Gene 2. Definition of Genes 3. The Gene as a Unit of Function (Cistron) 4. Gene as the Unit of Recombination (Recon) 5. The Gene as a Unit of Mutation (Muton) 6. Identification of Genetic Material.

  1. Introduction to the Modern Concept of Gene
  2. Definition of Genes
  3. The Gene as a Unit of Function (Cistron)
  4. Gene as the Unit of Recombination (Recon)
  5. The Gene as a Unit of Mutation (Muton)
  6. Identification of Genetic Material

1. Introduction to the Modern Concept of Gene:

Mendel while explaining the result of his breeding experiment pointed out that the hereditary characters were governed by some particulate genetic determiners present in the germ cells. The genetic determiners of heredity characters are now called ‘genes’. The term gene was coined by Johannsen (1909). De Vries used the term ‘pangen’ and perhaps, from this word the term gene was derived.

In the old books of genetics the term ‘gene’ is treated as merely something which affects the phenotype and behaves as a particle. It should be noted here that nothing was said about the size, shape and chemical constitution of gene in old definitions.

After the rediscovery of Mendelian laws of heredity, the cytology advanced rapidly and reached to the stage where Mendel’s hypothetical hereditary factors could soon be correlated with the chromosomes on following grounds:

1. Like the chromosomes, Mendelian factors are carried singly in mature germ cells.

2. Like the chromosomes, the hereditary factors are brought together in pairs by fertilization.

3. Like the chromosomes they separate or segregate at the time of germ cell formation in different generations.

The only objection in treating the chromosomes equivalent to Mendelian factors is that the number of Mendelian factors in the organisms far exceeds the number of chromosomes. In 1902, Sutton and Boveri independently suggested the way out for this objection and considered the chromosomes as containers of Mendelian hereditary units.

They did not treat chromosome as single heredity unit. In 1914, Thomas Morgan was working with the fruitfly (drosophila melanogaster). He noted that the fruitfly in question had 4 pairs of chromosomes and the hereditary characters were too many. This fact led Morgan to propose gene theory.

The theory states that:

(i) Chromosomes are bearers of hereditary units or genes and each chromosome carries hundreds or thousands of genes.

(ii) The genes are arranged on the chromosomes in the linear order and on the specific regions or loci.

If it is considered that gene is specific particle, then it follows that the chromosome would be a linear array of such particles bound together by non-genetic linkers of some type. Such a morphological differentiation can be observed in the chromosomes under some special circumstances. When a chromosome is observed in the early stages of first meiotic prophase, it appears as a ‘string of beads’.

The thickened parts or beads of chromosomes are called chromomeres and the string or linker joining the chromomeres is known as chromonema (Fig. 19.1). At one time, chromomeres were treated as genes. But, this is an oversimplified view and is no longer held.

The banding pattern of salivary gland chromosome of Drosophila (Fig. 19.2) and chromosomal loops in the lampbrush chromosome (Fig. 19.3) of amphibian eggs are also suggestive of functional discontinuity.

Actually, the genie material is not different from other non-genic material in the chromosome.

It is, perhaps, suggested by the fact that genetic recombination can and does take place within genie as well as non-genic areas.

As both the operation and the physicochemical nature of gene are not known clearly, the gene can be defined best in terms of its effects. Efforts to formulate theoretical models or hypothesis of gene action have resulted in highly divergent opinions.

There are two schools of thought which define genes in different ways:

(i) According to one school of thought, the specific molecule of genie material controls each character.

The exponents of this school are Dobzhansky (1955) and Beadle (1955).

(ii) The other school under the leadership of Goldschmidt holds the view that the interactions between all the components of genome are responsible for the manifestation of characters.

Stadler (1955) points out that the differences of opinions arise because one school defines genes as “operational units” whose actions can be demonstrated experimentally and the other school defines the gene in a hypothetical physicochemical sense.

In hypothetical sense the gene of classical genetics is visualised as a discrete particle inherited in Mendelian fashion or as unit of function that occupies a definite locus in the chromosome and is responsible for the expression of a specific phenotypic character, e.g., genes for white colouration of flower in pea or those for length of pea plant etc.

According to Benzer’s classical concept, gene is the unit of function (cistron), a unit of recombination (recon) and a unit of mutation (muton).

A gene does not produce character by itself but it exercises the major control on the development of character. The genes produce gene products that, in turn, determine specific phenotype.

3. The Gene as a Unit of Function (Cistron):

The first link between a gene and gene product was established in 1909 when A.E. Garrod suggested that the gene product was a protein. This hypothesis ‘one gene-one protein’ was largely ignored until around 1940 when it was conclusively demonstrated by Beadle and Tatum (1941) that the genes directed the protein synthesis.

Encouraged by this link between gene and protein, investigators worked out the mechanisms by which information in DNA was translated into the structure of protein. Soon it became clear that DNA is first transcribed into RNA, which is subsequently translated into protein.

Garrod as well as some other investigators suggested that genes produce proteins that act as enzymes. One gene-one enzyme hypothesis has been interpreted in different ways.

Gene represents a particular sequence of nucleotides along DNA molecule (or occasionally RNA in certain viruses) that acts as a unit of inheritance. Since gene forms a messenger RNA molecule it can be said one gene-one messenger RNA. But in prokaryotes several genes form a single mRNA (polycistronic gene).

The concept expressed as one genes one protein has now been changed to one gene-one polypeptide, since an enzyme or a protein may contain one or more polypeptides. Stahl had defined gene as a polynucleotide sequence of DNA controlling the expression of a particular trait.

The gene as a unit of function thus represents a segment of DNA molecule and consists of a linear sequence of nucleotides which controls some cellular function.

The number of nucleotides in a gene may vary in different organisms. In Escherichia coli the cistron may contain 1500 base pairs but in some others it may contain as many as 30,000 nucleotides. Each cistron is responsible for coding one mRNA molecule which in tum codes for a polypeptide chain (enzyme or protein).

A cistron may have hundreds of units of mutation (mutons) and units of recombination (recons) within it. Therefore, cistrons occupy much greater area in chromosome as compared to mutons and recons.

4. Gene as the Unit of Recombination (Recon):

The classical studies on the genetics of Drosophila indicated that gene was the shortest segment of chromosome controlling phenotypic characters which could be separated from its adjacent segments during crossing over, i.e., the genes were those parts of chromosomes between which crossing over was possible and the crossing over was not supposed to take place within the gene.

But recent studies based on the tests for recombination in viruses have shown that in viral DNA strand crossing over could occur not only between the genes but also within the genes. One of the sub-units of gene has been called recon. It is the smallest unit capable of genetic recombination. Recombination studies on microbes indicate that structurally recon may have one or two pairs of nucleotides.

Benzer (1955) demonstrated crossing over within the gene in T4 bacteriophage. Phage T4 contains one linear chromosome. There are two strains of T4 phage wild strain producing smooth edged plaques and the r II mutant strain producing rough edged plaques. r-Il mutants are of several types.

Benzer found that two adjacent genes r ll A and r ll B were responsible for rough edged plaque character. Each gene forms a polypeptide and the two polypeptides form a protein. A change in the polypeptide chain would result in a change in the phenotypic expression.

R ll A and r ll B mutants may cross in E. coli. The progeny produced from the cross were analysed for the frequency of recombination and it was found that some phage particles were of normal type. This was possible only if crossing over occurred within the genes by which segments of A and B genes united to form normal wild genes.

5. The Gene as a Unit of Mutation (Muton):

Gene has also been defined as an unit of mutation. The smallest chromosomal unit capable of undergoing mutation has been called the muton. At molecular level a muton consists of one or many pairs of nucleotides within the DNA molecule. Mutation thus may be caused by a change in one or more nucleotides in the DNA molecule.

Muntzing (1961) defines a gene as small segment of chromosome having a unitary biochemical function and specific effect on the properties of individual. According to him the genes may also occur in the cytoplasmic bodies that are sometimes associated with chromosomes or even sometimes occurring free in the cytoplasm.

6. Identification of Genetic Material:

For understanding the nature of genes it is necessary to know the chemical and physical nature of genetic material. At the moment most of our knowledge about this comes from the studies on fungi, bacteria and viruses. Here everybody seems generally agreed on the fact that the genetic materials of lower organisms are similar to those of higher ones.

Before deciding the nature of hereditary material one should keep in mind the following three principal characteristics of the material responsible for inheritable traits:

1. It must contain all the information’s regarding cell structure, function, development and reproduction.

2. It must be able to replicate accurately so that the progeny cells inherit the same genetic features as the parent cells.

3. It must be capable of undergoing variation through recombination and mutations and exist in infinite forms, otherwise organisms would not be capable of change, and adaptations and evolution would not be possible.

Much of the chemistry of the genetic material was known before its significance in the genetics was recognised. In mid to late nineteenth century and early twentieth century scientists believed that the genetic instructions from the nucleus were carried to the cytoplasm by protein molecules that were folded into specific configuration.

But several spectacular discoveries during the past four decades have changed the old ideas and now Deoxyribonucleic acid (DNA) is considered as the genetic material. Following publication of Mendel’s work Johann Friedrich Miescher in 1869 isolated a novel phosphorus bearing compound and named that as nuclein.

Miescher and other scientists subsequently demonstrated that the nuclei of all cellular organisms contain nuclein and nuclein was an important constituent of chromosomes. Chromosomes consist of 60% protein and 40% DNA. The following seven direct and indirect evidences from different sources have established that DNA is the essential genetic material (Lima de Faria and Moses, 1966 and others).

1. In prokaryotic organisms (organisms lacking well organized nucleus and chromosomes) to which operationally viruses can also be included, the genetic material is DNA.

2. Deoxyribonucleic acid is confined almost to the chromosomes in the nuclei of eukaryotes. DNA is a stable macromolecule, the content of which is directly related to the chromosome number.

3. The amount of DNA per nucleus is species characteristic and the amount of DNA found in the gamete is only half of the amount of DNA present in the somatic cells of all the members of a species. The diploid condition is restored only after fertilization.

Careful measurements of the amount of DNA and proteins in somatic cells and sperm cells indicated that DNA only played hereditary role .and not protein. The measurements indicated that the amounts of protein in sperms and somatic cells bore no definite relationship with each other whereas the amount of DNA in sperms was exactly one-half that in somatic cells.

4. Genes are characterized as self-perpetuating units, DNA molecules too replicate themselves and in the process of replication the old DNA acts as template for new one.

5. The highest efficiency of mutagenesis by ultraviolet light is at the wavelength of2600 A which is also wavelength of peak absorption by DNA.

6. The genetic transformation in bacteria is mediated by DNA. The most convincing evidence in support of the fact that genie material is DNA could appear in 1944 when Avery, MacLeod, and McCarty reported their work on transformation in Pneumococcus.

7. Hershey and Chase (1952) confirmed that in bacterial viruses (bacteriophages) the genetic material is DNA. Certain RNA viruses are exceptions in which the transfer of genetic information has been taken over by ribonucleic acid. Fraenkel Conrat (1955) working on the reproduction of Tobacco mosaic virus (TMV) proved that the hereditary material in that virus was definitely RNA.

The major experiments which established that DNA is genetic material are discussed here in to brief:

1. Transformation Experiment in Bacteria:

Frederick Griffith (1928) for the first time demonstrated genetic transformation in bacterium diplococcus pneumoniae, now named Streptococcus pneumoniae and Avery, MacLeod and McCarty (1944) later showed that DNA and not the protein, was the carrier of hereditary characters in diplococcus pneumoniae or Pneumococcus. This bacterium causes pneumonia in mice and men. There are two strains of Pneumococcus.

In one strain, capsule layer (slime coat) is formed of a polysaccharide material and colonies are shining and “smooth” (‘S’ strain). In other strain, cells lack polysaccharide slime layer and colonies formed by such cells are irregular or “rough” (‘R’ strain). Smooth (S) cells are virulent and cause Pneumonia but rough (R) cells are non-virulent. ‘S’ Pneumococci are classified into types, such as, type I-S, type II-S, type III-S and so on.

The cell of ‘S’ colony may change occasionally into ‘R’ bacterium but the reverse change (i.e., from R to S) is almost never seen. R cells upon division always give rise to R cells. In the course of his experiment. Griffith injected mice with living II-R Pneumococci and found that the mice did not suffer.

But when the mice were injected with live III-S type they suffered by pneumonia and died and when heat killed III-S bacteria were injected the mice did not suffer.

However, when the mixture of living cells of non-virulent II-R and heat killed III- S cells were injected into the mice, the mice unexpectedly developed pneumonia and died.

Post­mortem examination of dead mice showed the presence of both II-R and III-S type of pneumococci in the heart blood and this led Griffith to conclude that something released from the heat killed III-S cells was taken up by the avirulent R type cells which might have caused genetic transformation of living II-R bacteria into virulent cells (Fig. 19.4).

Avery and his associates at the Rock-feller Institute earnestly pursued to identify the transforming principle. Between 1930 and 1933 they demonstrated transformation in vitro rather than in the mice. They disintegrated encapsulated cells of type III-S and separated various chemical components (carbohydrates, proteins, fats, DNA, RNA etc.).

Then they took R-H cells derived from type II-S and mixed them separately with different chemical components of III-S cells. Avery and his associates observed that the DNA fraction was able to change some of the R cells (non-capsulated) to encapsulated S cells. The transformed R-II cells were like III-S and were similar in all respects to the cells from which the DNA fraction was taken (Fig. 19.5).

In 1944, Avery, MacLeod and McCarty published a remarkable paper in which they reported that they had purified the transforming principle. Analysis of the molecular composition and weight indicated that transforming factor was DNA.

They took S-type bacterium separated by centrifugation, killed them by heating, ruptured the cells in water and filtered. Filtrate salvaged was tested for its transforming ability, that was found to be positive. Filtrate was then treated with protease to degrade all proteins in that and tested for transforming ability which was found to be positive.

Next, the filtrate was treated with ribonucleic (RNAase) enzyme that digested all ribonucleic acid (RNA).

The filtrate salvaged was tested for its transforming power that was found to be positive. Finally the filtrate was treated with deoxyribo-nuclease (DNAase) which totally destroyed the DNA. The DNAase treated filtrate was tested for transforming ability, that was no longer able to convert R-type cells into virulent cells like III-S type.

The result of the experiment made avery and his colleagues to conclude that the transforming principle must be DNA. The idea was supported not only by the results of enzymatic digestion experiments but also by the analysis of purified transforming principle.

These experiments clearly indicate that the whole transforming ability resides in DNA. For this reason DNA of the cells is called the “transforming principle “. A variety of other hereditary characters in different species of bacteria have also been demonstrated to be governed by DNA.

The bacterial strains which are sensitive to antibiotics like penicillin or streptomycin can acquire permanent resistance to these antibiotics by transformation of DNA.

2. Bacteriophage Multiplication:

Another evidence in support of the fact that DNA is genetic material comes from the study of bacteriophage multiplication.

The DNA is infective material in the virus. In the infection, the phage attaches itself to the bacterial cell wall and injects its DNA strand into the bacterial cytoplasm. Inside the bacterial cell the phage particle multiplies. During the process of phage multiplication many new strands of DNA and protein sheaths are synthesised and hundred or so new phage particles resembling the original one are formed.

Phage multiplication is immediately followed by death or lysis of the infected bacterial cell. The newly born phage particles attach with the other adjacent bacterial cells and produce a region of lysis in the bacterial colony.

If the two components (DNA and Protein) of bacteriophage are separated mechanically and they are separately injected in the uninfected bacterial cells, then the new phage particles with both DNA and protein sheath will continue to be produced inside the cell in which virus DNA was injected, whereas no viral particle will be produced from the cell in which viral protein was injected.

The “Waring Blender Experiment” by Hershey and Chase in which they utilized the radioactive isotope P 32 to label DNA and s 35 to label protein of the bacterial virus T2 and showed that during infection of bacterial cell by virus only DNA entered the cell while the protein remained outside (Fig. 19.6). It is evident from the experiment that DNA is hereditary material and protein is non- hereditary.

If two genetically different phage particles differing in such characters as the sizes of the plaques of dead bacteria they form simultaneously infect the same bacterial cell, recombinant phage particles may be formed. Since in the infection only the DNA strands of virus particles entered the bacterial cell, it can be inferred that only DNA is genetic material.

3. Bacterial Conjugation:

A convincing evidence for DNA as genetic material has come from the process of bacterial conjugation. Laderberg and Tatum (1946) found that when F + (male) strains of Escherichia coli conjugate with F – (female) cells there is an unidirectional flow of F + factor from male cells to F – female cells so that the latter is converted into F – from male strain.

The F + factor is found to be a fragment of DNA molecule which occurs in the cytoplasm of bacterium.

4. RNA as the Genetic Material in Some Viruses:

Tobacco mosaic virus (TMV) which causes mosaic disease in tobacco consists of an outer protein coat and an inner core of nucleic acid RNA (Fig. 19.7). In 1955, Fraenkel Conrat fractionated RNA and protein of TMV and injected them separately into two healthy tobacco plants.

In this experiment they observed that viral RNA, completely free from its protein, could produce new virus particles which also caused mosaic disease in tobacco plant. The inoculation of viral protein did not produce the disease symptoms at all. This experiment showed that viral RNA alone can direct the formation of normal virus (Fig. 19.7).

Different strains of TMV are now known which produce different inherited lesions on tobacco leaves. The common virus (TMV-common) produces green, mosaic disease and a mutant TMV strain, TMV-HR (holmes ribgrass) produces ring-spot lesions. The amino-acid compositions of the protein sheaths of two strains are found to be different.

Heinz Fraenkel Conrat and Bea Singer isolated the RNA and proteins of two different strains of TMV and then they developed techniques to reassemble or reconstitute functional viruses with the RNA from TMV-common enclosed in protein sheath of TMV-HR and vice-versa (Fig. 19.7).

When the reconstituted viruses were allowed to infect tobacco leaves, the progeny viruses obtained from the infected leaves were always found to be the phenotypically and genotypically identical to parent strain from which RNA had been obtained.

The reconstituted viruses with RNA of TMV-common and protein sheath of TMV-HR produced green mosaic disease symptoms of TMV-common and protein characteristic of recovered progeny resembled that of TMV-common.

Similarly the reconstituted viruses with RNA of TMV-HR and Protein sheath of TMV-common produced ring spot lesions and the virus progeny had protein characteristic of TMV-HR. Thus it becomes clear that the source of RNA determined the nature of mosaic infection as well as the nature of proteins of progeny viruses. Hence, it is RNA in the plant viruses that carry genetic information and not the proteins.

The above experiments provide evidence in support of the fact that usually DNA, (excepting a few RNA viruses) is the genetic substance.

Viruses share genes with organisms across the tree of life, study finds

A new study finds that viruses share some genes exclusively with cells that are not their hosts. The study, reported in the journal Frontiers in Microbiology, adds to the evidence that viruses swap genes with a variety of cellular organisms and are agents of diversity, researchers say.

The study looked at protein structures in viruses and across all superkingdoms, or domains, of life: from the single-celled microbes known as bacteria and archaea, to eukaryotes, a group that includes animals, plants, fungi and all other living things.

"It is typical to define viruses in relation to their hosts, but this practice restricts our understanding of virus-cell interactions," said University of Illinois and COMSATS Institute of Information Technology researcher Arshan Nasir, who led the new research with Gustavo Caetano-Anolles, a professor of crop sciences and affiliate of the Carl R. Woese Institute for Genomic Biology at the U. of I., and Kyung Mo Kim, a senior scientist at the Korea Polar Research Institute, in Incheon, South Korea.

"Recent research has revealed that organisms can form partnerships with other organisms and live in communities. For example, many bacterial and archaeal species reside in and on the human body and constitute the human microbiota," Nasir said.

Viruses that infect archaea and bacteria, for example, are not known to infect eukarya. However, they may still interact in nonharmful ways with organisms they do not infect, the researchers said.

"We wanted to investigate the genomes of viruses and cellular organisms to look for possible traces of gene transfer from viruses to cells, beyond what we already know about virus interactions with their hosts," Nasir said.

The team used a bioinformatics approach to analyze the genomes of organisms and the viruses that infect them. Rather than focusing on genetic sequences, which can change over the generations, the team examined the functional components of proteins, which they call folds. Each fold -- and there are more than 1,400 of them across all domains of life -- has a unique 3-D structure that performs a specific operation. Because folds are critical to protein function, they remain stable even as the sequences that code for them change as a result of mutations or other processes, the researchers said.

"This makes protein folds reliable markers of evolutionary changes over vast time periods, especially for viruses that mutate notoriously fast," Nasir said.

The researchers found hundreds of folds that are present across all superkingdoms of life and in all types of viruses, which suggests that they came from an ancient ancestor of all life forms, Caetano-Anolles said.

Some folds, however, occur only within a single superkingdom and the viruses that infect it, suggesting a transfer of genetic material only between that group of viruses and their hosts. Out of a total of about 2,000 superfamilies of folds, the team found one that was exclusive to archaea and the viruses that infect archaea, 29 shared only by bacteria and the viruses that infect them, and 37 that are exclusive to eukaryotes and their viruses.

The data also point to other, as yet unknown, mechanisms that allow viruses to exchange genetic material with cells, the researchers said.

"We discovered many virus-hallmark genes in cellular organisms those viruses are not known to infect," Nasir said. "This was especially obvious for bacterial viruses and eukaryotic organisms, possibly because of the greater number of ways bacteria interact with eukarya."

"While people tend to think only about viruses that infect and kill their hosts, we have known for decades that a virus will sometimes enter into a cell and incorporate its genetic material into the cell without killing it," Caetano-Anolles said. In the case of single-celled organisms, those genes are sometimes passed along to future generations, he said.

Human DNA, too, contains remnants of viruses.

"Some retroelements and transposons, for example, are believed to have originated in ancient viruses," Nasir said. Retroelements are sequences copied from RNA viruses into DNA and inserted into the genomes of nonviral organisms. Transposons, also known as "jumping genes," can move from one part of the genome to another.

"If you have an entity that was a virus at some point and got co-opted into the genome, that becomes a part of the molecular heritage of the organism," Caetano-Anolles said.

The team also discovered a large subset of virus-specific protein folds that were not present in any cellular genomes.

"This suggests that viruses can create new genes and, potentially, transfer those genes to cellular organisms," Nasir said.

RNA Viruses, Evolution of

Genome-Scale Evolution

The Evolution of Genome Structure and Size

RNA viruses exhibit a huge diversity of genome structures, including those with positive- and negative-sense orientations, those with single or double strands of RNA, and those with single or multiple segments. Despite such diversity, it is possible that all these forms of genome organization have evolved as ways of controlling gene expression ( Holmes, 2009a ). Interestingly, recent studies have revealed important phylogenetic links between segmented and unsegmented RNA viruses ( Qin et al., 2014 ), and shown that genome segmentation may allow RNA viruses to explore a greater proportion of sequence space than when only a single segment is present ( Moreno et al., 2014 ).

In contrast, the genome sizes of known RNA viruses exhibit relatively little variation, from less 2500 nucleotides (nt) in the case of some mitoviruses to approximately 32 Kb in the Nidovirales, with a mean value of approximately 10 000 nt. One theory is that genome sizes are constrained by the maximum size of the genomic material that can be contained within a virion. However, there is a remarkably strong (allometric) relationship between viral genome and virion sizes that covers viruses of all sizes and types (including RNA and DNA), indicating that viral genomes expand in size along with their virions ( Cui et al., 2014 Figure 2 ). A more plausible explanation is therefore that genome sizes are set by (high) background mutation rates, particularly as there is a strong relationship between mutation rate and genome size (see below Gago et al., 2009 ).

Figure 2 . The relationship between the genome and virion sizes of viruses. RNA viruses are shown in red and DNA viruses in blue. Virion sizes, displayed as volume (nm 3 ) on a log scale, are shown on the y-axis, while genome length (kb) on a log scale is shown on the x-axis. The black line depicts the linear regression between log–log transformed data. The gray area shows the 95% confidence interval for the linear regression, while the outer gray lines represent the 95% prediction interval.

Reproduced from Cui, J., Schlub, T., Holmes, E.C., 2014. An allometric relationship between the genome length and virion volume of viruses. Journal of Virology 88, 6403–6410.

Mechanisms of Genome Evolution

Whatever the reasons for the genomic diversity in RNA viruses , a number of major evolutionary processes have been at play, although at uncertain frequencies and with complex patterns. For example, while gene duplication must be responsible for some of the genomic and functional diversity seen in RNA viruses, particularly in the creation of different viral families, it has been relatively rarely documented ( Simon-Loriere and Holmes, 2013 ). Importantly, more refined homology searching has revealed additional examples ( Kuchibhatla et al., 2014 ). It is possible that the relatively low frequency of gene duplication may reflect the major fitness costs (i.e., deleterious mutation load) associated with increases in genome size (see below). Lateral gene transfer (LGT) also appears to be a relatively rare event in RNA viruses ( Song et al., 2013 ), perhaps because it will similarly result in larger genomes. However, LGT has now been shown to have played a key role in the genesis of some virus groups ( Liu et al., 2012 ), and so may have generated important biodiversity. In addition, LGT can occasionally occur among between viruses and hosts with, for example, reports of RNA viruses incorporating host genome sequences ( Megens et al., 2014 ). A related theory is that of ‘modular evolution,’ in which viral genomes are proposed to comprise functional modules that can be exchanged through recombination to create novel viruses ( Botstein, 1980 ), although its role in RNA virus evolution remains uncertain.


The word is from the Latin neuter vīrus referring to poison and other noxious liquids, from the same Indo-European base as Sanskrit viṣa, Avestan vīša, and ancient Greek ἰός (all meaning "poison"), first attested in English in 1398 in John Trevisa's translation of Bartholomeus Anglicus's De Proprietatibus Rerum. [14] [15] Virulent, from Latin virulentus (poisonous), dates to c. 1400. [16] [17] A meaning of "agent that causes infectious disease" is first recorded in 1728, [15] long before the discovery of viruses by Dmitri Ivanovsky in 1892. The English plural is viruses (sometimes also vira), [18] whereas the Latin word is a mass noun, which has no classically attested plural (vīra is used in Neo-Latin [19] ). The adjective viral dates to 1948. [20] The term virion (plural virions), which dates from 1959, [21] is also used to refer to a single viral particle that is released from the cell and is capable of infecting other cells of the same type. [22]

Louis Pasteur was unable to find a causative agent for rabies and speculated about a pathogen too small to be detected by microscopes. [23] In 1884, the French microbiologist Charles Chamberland invented the Chamberland filter (or Pasteur-Chamberland filter) with pores small enough to remove all bacteria from a solution passed through it. [24] In 1892, the Russian biologist Dmitri Ivanovsky used this filter to study what is now known as the tobacco mosaic virus: crushed leaf extracts from infected tobacco plants remained infectious even after filtration to remove bacteria. Ivanovsky suggested the infection might be caused by a toxin produced by bacteria, but he did not pursue the idea. [25] At the time it was thought that all infectious agents could be retained by filters and grown on a nutrient medium—this was part of the germ theory of disease. [4] In 1898, the Dutch microbiologist Martinus Beijerinck repeated the experiments and became convinced that the filtered solution contained a new form of infectious agent. [26] He observed that the agent multiplied only in cells that were dividing, but as his experiments did not show that it was made of particles, he called it a contagium vivum fluidum (soluble living germ) and reintroduced the word virus. Beijerinck maintained that viruses were liquid in nature, a theory later discredited by Wendell Stanley, who proved they were particulate. [25] In the same year, Friedrich Loeffler and Paul Frosch passed the first animal virus, aphthovirus (the agent of foot-and-mouth disease), through a similar filter. [27]

In the early 20th century, the English bacteriologist Frederick Twort discovered a group of viruses that infect bacteria, now called bacteriophages [28] (or commonly 'phages'), and the French-Canadian microbiologist Félix d'Herelle described viruses that, when added to bacteria on an agar plate, would produce areas of dead bacteria. He accurately diluted a suspension of these viruses and discovered that the highest dilutions (lowest virus concentrations), rather than killing all the bacteria, formed discrete areas of dead organisms. Counting these areas and multiplying by the dilution factor allowed him to calculate the number of viruses in the original suspension. [29] Phages were heralded as a potential treatment for diseases such as typhoid and cholera, but their promise was forgotten with the development of penicillin. The development of bacterial resistance to antibiotics has renewed interest in the therapeutic use of bacteriophages. [30]

By the end of the 19th century, viruses were defined in terms of their infectivity, their ability to pass filters, and their requirement for living hosts. Viruses had been grown only in plants and animals. In 1906 Ross Granville Harrison invented a method for growing tissue in lymph, and in 1913 E. Steinhardt, C. Israeli, and R.A. Lambert used this method to grow vaccinia virus in fragments of guinea pig corneal tissue. [31] In 1928, H. B. Maitland and M. C. Maitland grew vaccinia virus in suspensions of minced hens' kidneys. Their method was not widely adopted until the 1950s when poliovirus was grown on a large scale for vaccine production. [32]

Another breakthrough came in 1931 when the American pathologist Ernest William Goodpasture and Alice Miles Woodruff grew influenza and several other viruses in fertilised chicken eggs. [33] In 1949, John Franklin Enders, Thomas Weller, and Frederick Robbins grew poliovirus in cultured cells from aborted human embryonic tissue, [34] the first virus to be grown without using solid animal tissue or eggs. This work enabled Hilary Koprowski, and then Jonas Salk, to make an effective polio vaccine. [35]

The first images of viruses were obtained upon the invention of electron microscopy in 1931 by the German engineers Ernst Ruska and Max Knoll. [36] In 1935, American biochemist and virologist Wendell Meredith Stanley examined the tobacco mosaic virus and found it was mostly made of protein. [37] A short time later, this virus was separated into protein and RNA parts. [38] The tobacco mosaic virus was the first to be crystallised and its structure could, therefore, be elucidated in detail. The first X-ray diffraction pictures of the crystallised virus were obtained by Bernal and Fankuchen in 1941. Based on her X-ray crystallographic pictures, Rosalind Franklin discovered the full structure of the virus in 1955. [39] In the same year, Heinz Fraenkel-Conrat and Robley Williams showed that purified tobacco mosaic virus RNA and its protein coat can assemble by themselves to form functional viruses, suggesting that this simple mechanism was probably the means through which viruses were created within their host cells. [40]

The second half of the 20th century was the golden age of virus discovery, and most of the documented species of animal, plant, and bacterial viruses were discovered during these years. [41] In 1957 equine arterivirus and the cause of Bovine virus diarrhoea (a pestivirus) were discovered. In 1963 the hepatitis B virus was discovered by Baruch Blumberg, [42] and in 1965 Howard Temin described the first retrovirus. Reverse transcriptase, the enzyme that retroviruses use to make DNA copies of their RNA, was first described in 1970 by Temin and David Baltimore independently. [43] In 1983 Luc Montagnier's team at the Pasteur Institute in France, first isolated the retrovirus now called HIV. [44] In 1989 Michael Houghton's team at Chiron Corporation discovered Hepatitis C. [45] [46]

Viruses are found wherever there is life and have probably existed since living cells first evolved. [47] The origin of viruses is unclear because they do not form fossils, so molecular techniques are used to investigate how they arose. [48] In addition, viral genetic material occasionally integrates into the germline of the host organisms, by which they can be passed on vertically to the offspring of the host for many generations. This provides an invaluable source of information for paleovirologists to trace back ancient viruses that have existed up to millions of years ago. There are three main hypotheses that aim to explain the origins of viruses: [49] [50]

Regressive hypothesis Viruses may have once been small cells that parasitised larger cells. Over time, genes not required by their parasitism were lost. The bacteria rickettsia and chlamydia are living cells that, like viruses, can reproduce only inside host cells. They lend support to this hypothesis, as their dependence on parasitism is likely to have caused the loss of genes that enabled them to survive outside a cell. This is also called the 'degeneracy hypothesis', [51] [52] or 'reduction hypothesis'. [53] Cellular origin hypothesis Some viruses may have evolved from bits of DNA or RNA that "escaped" from the genes of a larger organism. The escaped DNA could have come from plasmids (pieces of naked DNA that can move between cells) or transposons (molecules of DNA that replicate and move around to different positions within the genes of the cell). [54] Once called "jumping genes", transposons are examples of mobile genetic elements and could be the origin of some viruses. They were discovered in maize by Barbara McClintock in 1950. [55] This is sometimes called the 'vagrancy hypothesis', [51] [56] or the 'escape hypothesis'. [53] Co-evolution hypothesis This is also called the 'virus-first hypothesis' [53] and proposes that viruses may have evolved from complex molecules of protein and nucleic acid at the same time that cells first appeared on Earth and would have been dependent on cellular life for billions of years. Viroids are molecules of RNA that are not classified as viruses because they lack a protein coat. They have characteristics that are common to several viruses and are often called subviral agents. [57] Viroids are important pathogens of plants. [58] They do not code for proteins but interact with the host cell and use the host machinery for their replication. [59] The hepatitis delta virus of humans has an RNA genome similar to viroids but has a protein coat derived from hepatitis B virus and cannot produce one of its own. It is, therefore, a defective virus. Although hepatitis delta virus genome may replicate independently once inside a host cell, it requires the help of hepatitis B virus to provide a protein coat so that it can be transmitted to new cells. [60] In similar manner, the sputnik virophage is dependent on mimivirus, which infects the protozoan Acanthamoeba castellanii. [61] These viruses, which are dependent on the presence of other virus species in the host cell, are called 'satellites' and may represent evolutionary intermediates of viroids and viruses. [62] [63]

In the past, there were problems with all of these hypotheses: the regressive hypothesis did not explain why even the smallest of cellular parasites do not resemble viruses in any way. The escape hypothesis did not explain the complex capsids and other structures on virus particles. The virus-first hypothesis contravened the definition of viruses in that they require host cells. [53] Viruses are now recognised as ancient and as having origins that pre-date the divergence of life into the three domains. [64] This discovery has led modern virologists to reconsider and re-evaluate these three classical hypotheses. [64]

The evidence for an ancestral world of RNA cells [65] and computer analysis of viral and host DNA sequences are giving a better understanding of the evolutionary relationships between different viruses and may help identify the ancestors of modern viruses. To date, such analyses have not proved which of these hypotheses is correct. [65] It seems unlikely that all currently known viruses have a common ancestor, and viruses have probably arisen numerous times in the past by one or more mechanisms. [66]

Life properties

Scientific opinions differ on whether viruses are a form of life or organic structures that interact with living organisms. [11] They have been described as "organisms at the edge of life", [10] since they resemble organisms in that they possess genes, evolve by natural selection, [67] and reproduce by creating multiple copies of themselves through self-assembly. Although they have genes, they do not have a cellular structure, which is often seen as the basic unit of life. Viruses do not have their own metabolism and require a host cell to make new products. They therefore cannot naturally reproduce outside a host cell [68] —although some bacteria such as rickettsia and chlamydia are considered living organisms despite the same limitation. [69] [70] Accepted forms of life use cell division to reproduce, whereas viruses spontaneously assemble within cells. They differ from autonomous growth of crystals as they inherit genetic mutations while being subject to natural selection. Virus self-assembly within host cells has implications for the study of the origin of life, as it lends further credence to the hypothesis that life could have started as self-assembling organic molecules. [2]


Viruses display a wide diversity of shapes and sizes, called 'morphologies'. In general, viruses are much smaller than bacteria. Most viruses that have been studied have a diameter between 20 and 300 nanometres. Some filoviruses have a total length of up to 1400 nm their diameters are only about 80 nm. [71] Most viruses cannot be seen with an optical microscope, so scanning and transmission electron microscopes are used to visualise them. [72] To increase the contrast between viruses and the background, electron-dense "stains" are used. These are solutions of salts of heavy metals, such as tungsten, that scatter the electrons from regions covered with the stain. When virions are coated with stain (positive staining), fine detail is obscured. Negative staining overcomes this problem by staining the background only. [73]

A complete virus particle, known as a virion, consists of nucleic acid surrounded by a protective coat of protein called a capsid. These are formed from protein subunits called capsomeres. [74] Viruses can have a lipid "envelope" derived from the host cell membrane. The capsid is made from proteins encoded by the viral genome and its shape serves as the basis for morphological distinction. [75] [76] Virally-coded protein subunits will self-assemble to form a capsid, in general requiring the presence of the virus genome. Complex viruses code for proteins that assist in the construction of their capsid. Proteins associated with nucleic acid are known as nucleoproteins, and the association of viral capsid proteins with viral nucleic acid is called a nucleocapsid. The capsid and entire virus structure can be mechanically (physically) probed through atomic force microscopy. [77] [78] In general, there are five main morphological virus types:

Helical These viruses are composed of a single type of capsomere stacked around a central axis to form a helical structure, which may have a central cavity, or tube. This arrangement results in virions which can be short and highly rigid rods, or long and very flexible filaments. The genetic material (typically single-stranded RNA, but single-stranded DNA in some cases) is bound into the protein helix by interactions between the negatively charged nucleic acid and positive charges on the protein. Overall, the length of a helical capsid is related to the length of the nucleic acid contained within it, and the diameter is dependent on the size and arrangement of capsomeres. The well-studied tobacco mosaic virus [79] and inovirus [80] are examples of helical viruses. Icosahedral Most animal viruses are icosahedral or near-spherical with chiral icosahedral symmetry. A regular icosahedron is the optimum way of forming a closed shell from identical subunits. The minimum number of capsomeres required for each triangular face is 3, which gives 60 for the icosahedron. Many viruses, such as rotavirus, have more than 60 capsomers and appear spherical but they retain this symmetry. To achieve this, the capsomeres at the apices are surrounded by five other capsomeres and are called pentons. Capsomeres on the triangular faces are surrounded by six others and are called hexons. [81] Hexons are in essence flat and pentons, which form the 12 vertices, are curved. The same protein may act as the subunit of both the pentamers and hexamers or they may be composed of different proteins. [82] Prolate This is an icosahedron elongated along the fivefold axis and is a common arrangement of the heads of bacteriophages. This structure is composed of a cylinder with a cap at either end. [83] Enveloped Some species of virus envelop themselves in a modified form of one of the cell membranes, either the outer membrane surrounding an infected host cell or internal membranes such as a nuclear membrane or endoplasmic reticulum, thus gaining an outer lipid bilayer known as a viral envelope. This membrane is studded with proteins coded for by the viral genome and host genome the lipid membrane itself and any carbohydrates present originate entirely from the host. Influenza virus, HIV (which causes AIDS), and severe acute respiratory syndrome coronavirus 2 (which causes COVID-19) [84] use this strategy. Most enveloped viruses are dependent on the envelope for their infectivity. [85] Complex These viruses possess a capsid that is neither purely helical nor purely icosahedral, and that may possess extra structures such as protein tails or a complex outer wall. Some bacteriophages, such as Enterobacteria phage T4, have a complex structure consisting of an icosahedral head bound to a helical tail, which may have a hexagonal base plate with protruding protein tail fibres. This tail structure acts like a molecular syringe, attaching to the bacterial host and then injecting the viral genome into the cell. [86]

The poxviruses are large, complex viruses that have an unusual morphology. The viral genome is associated with proteins within a central disc structure known as a nucleoid. The nucleoid is surrounded by a membrane and two lateral bodies of unknown function. The virus has an outer envelope with a thick layer of protein studded over its surface. The whole virion is slightly pleomorphic, ranging from ovoid to brick-shaped. [87]

Giant viruses

Mimivirus is one of the largest characterised viruses, with a capsid diameter of 400 nm. Protein filaments measuring 100 nm project from the surface. The capsid appears hexagonal under an electron microscope, therefore the capsid is probably icosahedral. [88] In 2011, researchers discovered the largest then known virus in samples of water collected from the ocean floor off the coast of Las Cruces, Chile. Provisionally named Megavirus chilensis, it can be seen with a basic optical microscope. [89] In 2013, the Pandoravirus genus was discovered in Chile and Australia, and has genomes about twice as large as Megavirus and Mimivirus. [90] All giant viruses have dsDNA genomes and they are classified into several families: Mimiviridae, Pithoviridae, Pandoraviridae, Phycodnaviridae, and the Mollivirus genus. [91]

Some viruses that infect Archaea have complex structures unrelated to any other form of virus, with a wide variety of unusual shapes, ranging from spindle-shaped structures to viruses that resemble hooked rods, teardrops or even bottles. Other archaeal viruses resemble the tailed bacteriophages, and can have multiple tail structures. [92]


  • DNA
  • RNA
  • Both DNA and RNA (at different stages in the life cycle)
  • Linear
  • Circular
  • Segmented
  • Single-stranded (ss)
  • Double-stranded (ds)
  • Double-stranded with regions of single-strandedness
  • Positive sense (+)
  • Negative sense (−)
  • Ambisense (+/−)

An enormous variety of genomic structures can be seen among viral species as a group, they contain more structural genomic diversity than plants, animals, archaea, or bacteria. There are millions of different types of viruses, [6] although fewer than 7,000 types have been described in detail. [93] As of January 2021, the NCBI Virus genome database has more than 193,000 complete genome sequences, [94] but there are doubtlessly many more to be discovered. [95] [96]

A virus has either a DNA or an RNA genome and is called a DNA virus or an RNA virus, respectively. The vast majority of viruses have RNA genomes. Plant viruses tend to have single-stranded RNA genomes and bacteriophages tend to have double-stranded DNA genomes. [97]

Viral genomes are circular, as in the polyomaviruses, or linear, as in the adenoviruses. The type of nucleic acid is irrelevant to the shape of the genome. Among RNA viruses and certain DNA viruses, the genome is often divided up into separate parts, in which case it is called segmented. For RNA viruses, each segment often codes for only one protein and they are usually found together in one capsid. All segments are not required to be in the same virion for the virus to be infectious, as demonstrated by brome mosaic virus and several other plant viruses. [71]

A viral genome, irrespective of nucleic acid type, is almost always either single-stranded (ss) or double-stranded (ds). Single-stranded genomes consist of an unpaired nucleic acid, analogous to one-half of a ladder split down the middle. Double-stranded genomes consist of two complementary paired nucleic acids, analogous to a ladder. The virus particles of some virus families, such as those belonging to the Hepadnaviridae, contain a genome that is partially double-stranded and partially single-stranded. [97]

For most viruses with RNA genomes and some with single-stranded DNA (ssDNA) genomes, the single strands are said to be either positive-sense (called the 'plus-strand') or negative-sense (called the 'minus-strand'), depending on if they are complementary to the viral messenger RNA (mRNA). Positive-sense viral RNA is in the same sense as viral mRNA and thus at least a part of it can be immediately translated by the host cell. Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA-dependent RNA polymerase before translation. DNA nomenclature for viruses with genomic ssDNA is similar to RNA nomenclature, in that positive-strand viral ssDNA is identical in sequence to the viral mRNA and is thus a coding strand, while negative-sense viral ssDNA is complementary to the viral mRNA and is thus a template strand. [97] Several types of ssDNA and ssRNA viruses have genomes that are ambisense in that transcription can occur off both strands in a double-stranded replicative intermediate. Examples include geminiviruses, which are ssDNA plant viruses and arenaviruses, which are ssRNA viruses of animals. [98]

Genome size

Genome size varies greatly between species. The smallest—the ssDNA circoviruses, family Circoviridae—code for only two proteins and have a genome size of only two kilobases [99] the largest—the pandoraviruses—have genome sizes of around two megabases which code for about 2500 proteins. [90] Virus genes rarely have introns and often are arranged in the genome so that they overlap. [100]

In general, RNA viruses have smaller genome sizes than DNA viruses because of a higher error-rate when replicating, and have a maximum upper size limit. [48] Beyond this, errors when replicating render the virus useless or uncompetitive. To compensate, RNA viruses often have segmented genomes—the genome is split into smaller molecules—thus reducing the chance that an error in a single-component genome will incapacitate the entire genome. In contrast, DNA viruses generally have larger genomes because of the high fidelity of their replication enzymes. [101] Single-strand DNA viruses are an exception to this rule, as mutation rates for these genomes can approach the extreme of the ssRNA virus case. [102]

Genetic mutation

Viruses undergo genetic change by several mechanisms. These include a process called antigenic drift where individual bases in the DNA or RNA mutate to other bases. Most of these point mutations are "silent"—they do not change the protein that the gene encodes—but others can confer evolutionary advantages such as resistance to antiviral drugs. [103] [104] Antigenic shift occurs when there is a major change in the genome of the virus. This can be a result of recombination or reassortment. When this happens with influenza viruses, pandemics might result. [105] RNA viruses often exist as quasispecies or swarms of viruses of the same species but with slightly different genome nucleoside sequences. Such quasispecies are a prime target for natural selection. [106]

Segmented genomes confer evolutionary advantages different strains of a virus with a segmented genome can shuffle and combine genes and produce progeny viruses (or offspring) that have unique characteristics. This is called reassortment or 'viral sex'. [107]

Genetic recombination is the process by which a strand of DNA is broken and then joined to the end of a different DNA molecule. This can occur when viruses infect cells simultaneously and studies of viral evolution have shown that recombination has been rampant in the species studied. [108] Recombination is common to both RNA and DNA viruses. [109] [110]

Replication cycle

Viral populations do not grow through cell division, because they are acellular. Instead, they use the machinery and metabolism of a host cell to produce multiple copies of themselves, and they assemble in the cell. [111] When infected, the host cell is forced to rapidly produce thousands of copies of the original virus. [112]

Their life cycle differs greatly between species, but there are six basic stages in their life cycle: [113]

Attachment is a specific binding between viral capsid proteins and specific receptors on the host cellular surface. This specificity determines the host range and type of host cell of a virus. For example, HIV infects a limited range of human leucocytes. This is because its surface protein, gp120, specifically interacts with the CD4 molecule—a chemokine receptor—which is most commonly found on the surface of CD4+ T-Cells. This mechanism has evolved to favour those viruses that infect only cells in which they are capable of replication. Attachment to the receptor can induce the viral envelope protein to undergo changes that result in the fusion of viral and cellular membranes, or changes of non-enveloped virus surface proteins that allow the virus to enter. [114]

Penetration or viral entry follows attachment: Virions enter the host cell through receptor-mediated endocytosis or membrane fusion. The infection of plant and fungal cells is different from that of animal cells. Plants have a rigid cell wall made of cellulose, and fungi one of chitin, so most viruses can get inside these cells only after trauma to the cell wall. [115] Nearly all plant viruses (such as tobacco mosaic virus) can also move directly from cell to cell, in the form of single-stranded nucleoprotein complexes, through pores called plasmodesmata. [116] Bacteria, like plants, have strong cell walls that a virus must breach to infect the cell. Given that bacterial cell walls are much thinner than plant cell walls due to their much smaller size, some viruses have evolved mechanisms that inject their genome into the bacterial cell across the cell wall, while the viral capsid remains outside. [117]

Uncoating is a process in which the viral capsid is removed: This may be by degradation by viral enzymes or host enzymes or by simple dissociation the end-result is the releasing of the viral genomic nucleic acid. [118]

Replication of viruses involves primarily multiplication of the genome. Replication involves the synthesis of viral messenger RNA (mRNA) from "early" genes (with exceptions for positive-sense RNA viruses), viral protein synthesis, possible assembly of viral proteins, then viral genome replication mediated by early or regulatory protein expression. This may be followed, for complex viruses with larger genomes, by one or more further rounds of mRNA synthesis: "late" gene expression is, in general, of structural or virion proteins. [119]

Assembly – Following the structure-mediated self-assembly of the virus particles, some modification of the proteins often occurs. In viruses such as HIV, this modification (sometimes called maturation) occurs after the virus has been released from the host cell. [120]

Release – Viruses can be released from the host cell by lysis, a process that kills the cell by bursting its membrane and cell wall if present: this is a feature of many bacterial and some animal viruses. Some viruses undergo a lysogenic cycle where the viral genome is incorporated by genetic recombination into a specific place in the host's chromosome. The viral genome is then known as a "provirus" or, in the case of bacteriophages a "prophage". [121] Whenever the host divides, the viral genome is also replicated. The viral genome is mostly silent within the host. At some point, the provirus or prophage may give rise to the active virus, which may lyse the host cells. [122] Enveloped viruses (e.g., HIV) typically are released from the host cell by budding. During this process, the virus acquires its envelope, which is a modified piece of the host's plasma or other, internal membrane. [123]

Genome replication

The genetic material within virus particles, and the method by which the material is replicated, varies considerably between different types of viruses.

DNA viruses The genome replication of most DNA viruses takes place in the cell's nucleus. If the cell has the appropriate receptor on its surface, these viruses enter the cell either by direct fusion with the cell membrane (e.g., herpesviruses) or—more usually—by receptor-mediated endocytosis. Most DNA viruses are entirely dependent on the host cell's DNA and RNA synthesising machinery and RNA processing machinery. Viruses with larger genomes may encode much of this machinery themselves. In eukaryotes, the viral genome must cross the cell's nuclear membrane to access this machinery, while in bacteria it need only enter the cell. [124] RNA viruses Replication of RNA viruses usually takes place in the cytoplasm. RNA viruses can be placed into four different groups depending on their modes of replication. The polarity (whether or not it can be used directly by ribosomes to make proteins) of single-stranded RNA viruses largely determines the replicative mechanism the other major criterion is whether the genetic material is single-stranded or double-stranded. All RNA viruses use their own RNA replicase enzymes to create copies of their genomes. [125] Reverse transcribing viruses Reverse transcribing viruses have ssRNA (Retroviridae, Metaviridae, Pseudoviridae) or dsDNA (Caulimoviridae, and Hepadnaviridae) in their particles. Reverse transcribing viruses with RNA genomes (retroviruses) use a DNA intermediate to replicate, whereas those with DNA genomes (pararetroviruses) use an RNA intermediate during genome replication. Both types use a reverse transcriptase, or RNA-dependent DNA polymerase enzyme, to carry out the nucleic acid conversion. Retroviruses integrate the DNA produced by reverse transcription into the host genome as a provirus as a part of the replication process pararetroviruses do not, although integrated genome copies of especially plant pararetroviruses can give rise to infectious virus. [126] They are susceptible to antiviral drugs that inhibit the reverse transcriptase enzyme, e.g. zidovudine and lamivudine. An example of the first type is HIV, which is a retrovirus. Examples of the second type are the Hepadnaviridae, which includes Hepatitis B virus. [127]

Cytopathic effects on the host cell

The range of structural and biochemical effects that viruses have on the host cell is extensive. [128] These are called 'cytopathic effects'. [129] Most virus infections eventually result in the death of the host cell. The causes of death include cell lysis, alterations to the cell's surface membrane and apoptosis. [130] Often cell death is caused by cessation of its normal activities because of suppression by virus-specific proteins, not all of which are components of the virus particle. [131] The distinction between cytopathic and harmless is gradual. Some viruses, such as Epstein–Barr virus, can cause cells to proliferate without causing malignancy, [132] while others, such as papillomaviruses, are established causes of cancer. [133]

Dormant and latent infections

Some viruses cause no apparent changes to the infected cell. Cells in which the virus is latent and inactive show few signs of infection and often function normally. [134] This causes persistent infections and the virus is often dormant for many months or years. This is often the case with herpes viruses. [135] [136]

Host range

Viruses are by far the most abundant biological entities on Earth and they outnumber all the others put together. [137] They infect all types of cellular life including animals, plants, bacteria and fungi. [93] Different types of viruses can infect only a limited range of hosts and many are species-specific. Some, such as smallpox virus for example, can infect only one species—in this case humans, [138] and are said to have a narrow host range. Other viruses, such as rabies virus, can infect different species of mammals and are said to have a broad range. [139] The viruses that infect plants are harmless to animals, and most viruses that infect other animals are harmless to humans. [140] The host range of some bacteriophages is limited to a single strain of bacteria and they can be used to trace the source of outbreaks of infections by a method called phage typing. [141] The complete set of viruses in an organism or habitat is called the virome for example, all human viruses constitute the human virome. [142]

Classification seeks to describe the diversity of viruses by naming and grouping them on the basis of similarities. In 1962, André Lwoff, Robert Horne, and Paul Tournier were the first to develop a means of virus classification, based on the Linnaean hierarchical system. [143] This system based classification on phylum, class, order, family, genus, and species. Viruses were grouped according to their shared properties (not those of their hosts) and the type of nucleic acid forming their genomes. [144] In 1966, the International Committee on Taxonomy of Viruses (ICTV) was formed. The system proposed by Lwoff, Horne and Tournier was initially not accepted by the ICTV because the small genome size of viruses and their high rate of mutation made it difficult to determine their ancestry beyond order. As such, the Baltimore classification system has come to be used to supplement the more traditional hierarchy. [145] Starting in 2018, the ICTV began to acknowledge deeper evolutionary relationships between viruses that have been discovered over time and adopted a 15-rank classification system ranging from realm to species. [146]

ICTV classification

The ICTV developed the current classification system and wrote guidelines that put a greater weight on certain virus properties to maintain family uniformity. A unified taxonomy (a universal system for classifying viruses) has been established. Only a small part of the total diversity of viruses has been studied. [147] As of 2020, 6 realms, 10 kingdoms, 17 phyla, 2 subphyla, 39 classes, 59 orders, 8 suborders, 189 families, 136 subfamilies, 2,224 genera, 70 subgenera, and 9,110 species of viruses have been defined by the ICTV. [5]

The general taxonomic structure of taxon ranges and the suffixes used in taxonomic names are shown hereafter. As of 2020, the ranks of subrealm, subkingdom, and subclass are unused, whereas all other ranks are in use.

Realm (-viria) Subrealm (-vira) Kingdom (-virae) Subkingdom (-virites) Phylum (-viricota) Subphylum (-viricotina) Class (-viricetes) Subclass (-viricetidae) Order (-virales) Suborder (-virineae) Family (-viridae) Subfamily (-virinae) Genus (-virus) Subgenus (-virus) Species

Baltimore classification

The Nobel Prize-winning biologist David Baltimore devised the Baltimore classification system. [43] [148] The ICTV classification system is used in conjunction with the Baltimore classification system in modern virus classification. [149] [150] [151]

The Baltimore classification of viruses is based on the mechanism of mRNA production. Viruses must generate mRNAs from their genomes to produce proteins and replicate themselves, but different mechanisms are used to achieve this in each virus family. Viral genomes may be single-stranded (ss) or double-stranded (ds), RNA or DNA, and may or may not use reverse transcriptase (RT). In addition, ssRNA viruses may be either sense (+) or antisense (−). This classification places viruses into seven groups:

  • I: dsDNA viruses (e.g. Adenoviruses, Herpesviruses, Poxviruses)
  • II: ssDNA viruses (+ strand or "sense") DNA (e.g. Parvoviruses)
  • III: dsRNA viruses (e.g. Reoviruses)
  • IV: (+)ssRNA viruses (+ strand or sense) RNA (e.g. Coronaviruses, Picornaviruses, Togaviruses)
  • V: (−)ssRNA viruses (− strand or antisense) RNA (e.g. Orthomyxoviruses, Rhabdoviruses)
  • VI: ssRNA-RT viruses (+ strand or sense) RNA with DNA intermediate in life-cycle (e.g. Retroviruses)
  • VII: dsDNA-RT viruses DNA with RNA intermediate in life-cycle (e.g. Hepadnaviruses)

Examples of common human diseases caused by viruses include the common cold, influenza, chickenpox, and cold sores. Many serious diseases such as rabies, Ebola virus disease, AIDS (HIV), avian influenza, and SARS are caused by viruses. The relative ability of viruses to cause disease is described in terms of virulence. Other diseases are under investigation to discover if they have a virus as the causative agent, such as the possible connection between human herpesvirus 6 (HHV6) and neurological diseases such as multiple sclerosis and chronic fatigue syndrome. [153] There is controversy over whether the bornavirus, previously thought to cause neurological diseases in horses, could be responsible for psychiatric illnesses in humans. [154]

Viruses have different mechanisms by which they produce disease in an organism, which depends largely on the viral species. Mechanisms at the cellular level primarily include cell lysis, the breaking open and subsequent death of the cell. In multicellular organisms, if enough cells die, the whole organism will start to suffer the effects. Although viruses cause disruption of healthy homeostasis, resulting in disease, they may exist relatively harmlessly within an organism. An example would include the ability of the herpes simplex virus, which causes cold sores, to remain in a dormant state within the human body. This is called latency [155] and is a characteristic of the herpes viruses, including Epstein–Barr virus, which causes glandular fever, and varicella zoster virus, which causes chickenpox and shingles. Most people have been infected with at least one of these types of herpes virus. [156] These latent viruses might sometimes be beneficial, as the presence of the virus can increase immunity against bacterial pathogens, such as Yersinia pestis. [157]

Some viruses can cause lifelong or chronic infections, where the viruses continue to replicate in the body despite the host's defence mechanisms. [158] This is common in hepatitis B virus and hepatitis C virus infections. People chronically infected are known as carriers, as they serve as reservoirs of infectious virus. [159] In populations with a high proportion of carriers, the disease is said to be endemic. [160]


Viral epidemiology is the branch of medical science that deals with the transmission and control of virus infections in humans. Transmission of viruses can be vertical, which means from mother to child, or horizontal, which means from person to person. Examples of vertical transmission include hepatitis B virus and HIV, where the baby is born already infected with the virus. [161] Another, more rare, example is the varicella zoster virus, which, although causing relatively mild infections in children and adults, can be fatal to the foetus and newborn baby. [162]

Horizontal transmission is the most common mechanism of spread of viruses in populations. [163] Horizontal transmission can occur when body fluids are exchanged during sexual activity, by exchange of saliva or when contaminated food or water is ingested. It can also occur when aerosols containing viruses are inhaled or by insect vectors such as when infected mosquitoes penetrate the skin of a host. [163] Most types of viruses are restricted to just one or two of these mechanisms and they are referred to as "respiratory viruses" or "enteric viruses" and so forth. The rate or speed of transmission of viral infections depends on factors that include population density, the number of susceptible individuals, (i.e., those not immune), [164] the quality of healthcare and the weather. [165]

Epidemiology is used to break the chain of infection in populations during outbreaks of viral diseases. [166] Control measures are used that are based on knowledge of how the virus is transmitted. It is important to find the source, or sources, of the outbreak and to identify the virus. Once the virus has been identified, the chain of transmission can sometimes be broken by vaccines. When vaccines are not available, sanitation and disinfection can be effective. Often, infected people are isolated from the rest of the community, and those that have been exposed to the virus are placed in quarantine. [167] To control the outbreak of foot-and-mouth disease in cattle in Britain in 2001, thousands of cattle were slaughtered. [168] Most viral infections of humans and other animals have incubation periods during which the infection causes no signs or symptoms. [169] Incubation periods for viral diseases range from a few days to weeks, but are known for most infections. [170] Somewhat overlapping, but mainly following the incubation period, there is a period of communicability—a time when an infected individual or animal is contagious and can infect another person or animal. [170] This, too, is known for many viral infections, and knowledge of the length of both periods is important in the control of outbreaks. [171] When outbreaks cause an unusually high proportion of cases in a population, community, or region, they are called epidemics. If outbreaks spread worldwide, they are called pandemics. [172]

Epidemics and pandemics

A pandemic is a worldwide epidemic. The 1918 flu pandemic, which lasted until 1919, was a category 5 influenza pandemic caused by an unusually severe and deadly influenza A virus. The victims were often healthy young adults, in contrast to most influenza outbreaks, which predominantly affect juvenile, elderly, or otherwise-weakened patients. [173] Older estimates say it killed 40–50 million people, [174] while more recent research suggests that it may have killed as many as 100 million people, or 5% of the world's population in 1918. [175]

Although viral pandemics are rare events, HIV—which evolved from viruses found in monkeys and chimpanzees—has been pandemic since at least the 1980s. [176] During the 20th century there were four pandemics caused by influenza virus and those that occurred in 1918, 1957 and 1968 were severe. [177] Most researchers believe that HIV originated in sub-Saharan Africa during the 20th century [178] it is now a pandemic, with an estimated 37.9 million people now living with the disease worldwide. [179] There were about 770,000 deaths from AIDS in 2018. [180] The Joint United Nations Programme on HIV/AIDS (UNAIDS) and the World Health Organization (WHO) estimate that AIDS has killed more than 25 million people since it was first recognised on 5 June 1981, making it one of the most destructive epidemics in recorded history. [181] In 2007 there were 2.7 million new HIV infections and 2 million HIV-related deaths. [182]

Several highly lethal viral pathogens are members of the Filoviridae. Filoviruses are filament-like viruses that cause viral hemorrhagic fever, and include ebolaviruses and marburgviruses. Marburg virus, first discovered in 1967, attracted widespread press attention in April 2005 for an outbreak in Angola. [183] Ebola virus disease has also caused intermittent outbreaks with high mortality rates since 1976 when it was first identified. The worst and most recent one is the 2013–2016 West Africa epidemic. [184]

Except for smallpox, most pandemics are caused by newly evolved viruses. These "emergent" viruses are usually mutants of less harmful viruses that have circulated previously either in humans or other animals. [185]

Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) are caused by new types of coronaviruses. Other coronaviruses are known to cause mild infections in humans, [186] so the virulence and rapid spread of SARS infections—that by July 2003 had caused around 8,000 cases and 800 deaths—was unexpected and most countries were not prepared. [187]

A related coronavirus emerged in Wuhan, China in November 2019 and spread rapidly around the world. Thought to have originated in bats and subsequently named severe acute respiratory syndrome coronavirus 2, infections with the virus caused a pandemic in 2020. [188] [189] [190] Unprecedented restrictions in peacetime have been placed on international travel, [191] and curfews imposed in several major cities worldwide. [192]


Viruses are an established cause of cancer in humans and other species. Viral cancers occur only in a minority of infected persons (or animals). Cancer viruses come from a range of virus families, including both RNA and DNA viruses, and so there is no single type of "oncovirus" (an obsolete term originally used for acutely transforming retroviruses). The development of cancer is determined by a variety of factors such as host immunity [193] and mutations in the host. [194] Viruses accepted to cause human cancers include some genotypes of human papillomavirus, hepatitis B virus, hepatitis C virus, Epstein–Barr virus, Kaposi's sarcoma-associated herpesvirus and human T-lymphotropic virus. The most recently discovered human cancer virus is a polyomavirus (Merkel cell polyomavirus) that causes most cases of a rare form of skin cancer called Merkel cell carcinoma. [195] Hepatitis viruses can develop into a chronic viral infection that leads to liver cancer. [196] [197] Infection by human T-lymphotropic virus can lead to tropical spastic paraparesis and adult T-cell leukaemia. [198] Human papillomaviruses are an established cause of cancers of cervix, skin, anus, and penis. [199] Within the Herpesviridae, Kaposi's sarcoma-associated herpesvirus causes Kaposi's sarcoma and body-cavity lymphoma, and Epstein–Barr virus causes Burkitt's lymphoma, Hodgkin's lymphoma, B lymphoproliferative disorder, and nasopharyngeal carcinoma. [200] Merkel cell polyomavirus closely related to SV40 and mouse polyomaviruses that have been used as animal models for cancer viruses for over 50 years. [201]

Host defence mechanisms

The body's first line of defence against viruses is the innate immune system. This comprises cells and other mechanisms that defend the host from infection in a non-specific manner. This means that the cells of the innate system recognise, and respond to, pathogens in a generic way, but, unlike the adaptive immune system, it does not confer long-lasting or protective immunity to the host. [202]

RNA interference is an important innate defence against viruses. [203] Many viruses have a replication strategy that involves double-stranded RNA (dsRNA). When such a virus infects a cell, it releases its RNA molecule or molecules, which immediately bind to a protein complex called a dicer that cuts the RNA into smaller pieces. A biochemical pathway—the RISC complex—is activated, which ensures cell survival by degrading the viral mRNA. Rotaviruses have evolved to avoid this defence mechanism by not uncoating fully inside the cell, and releasing newly produced mRNA through pores in the particle's inner capsid. Their genomic dsRNA remains protected inside the core of the virion. [204] [205]

When the adaptive immune system of a vertebrate encounters a virus, it produces specific antibodies that bind to the virus and often render it non-infectious. This is called humoral immunity. Two types of antibodies are important. The first, called IgM, is highly effective at neutralising viruses but is produced by the cells of the immune system only for a few weeks. The second, called IgG, is produced indefinitely. The presence of IgM in the blood of the host is used to test for acute infection, whereas IgG indicates an infection sometime in the past. [206] IgG antibody is measured when tests for immunity are carried out. [207]

Antibodies can continue to be an effective defence mechanism even after viruses have managed to gain entry to the host cell. A protein that is in cells, called TRIM21, can attach to the antibodies on the surface of the virus particle. This primes the subsequent destruction of the virus by the enzymes of the cell's proteosome system. [208]

A second defence of vertebrates against viruses is called cell-mediated immunity and involves immune cells known as T cells. The body's cells constantly display short fragments of their proteins on the cell's surface, and, if a T cell recognises a suspicious viral fragment there, the host cell is destroyed by 'killer T' cells and the virus-specific T-cells proliferate. Cells such as the macrophage are specialists at this antigen presentation. [209] The production of interferon is an important host defence mechanism. This is a hormone produced by the body when viruses are present. Its role in immunity is complex it eventually stops the viruses from reproducing by killing the infected cell and its close neighbours. [210]

Not all virus infections produce a protective immune response in this way. HIV evades the immune system by constantly changing the amino acid sequence of the proteins on the surface of the virion. This is known as "escape mutation" as the viral epitopes escape recognition by the host immune response. These persistent viruses evade immune control by sequestration, blockade of antigen presentation, cytokine resistance, evasion of natural killer cell activities, escape from apoptosis, and antigenic shift. [211] Other viruses, called 'neurotropic viruses', are disseminated by neural spread where the immune system may be unable to reach them.

Prevention and treatment

Because viruses use vital metabolic pathways within host cells to replicate, they are difficult to eliminate without using drugs that cause toxic effects to host cells in general. The most effective medical approaches to viral diseases are vaccinations to provide immunity to infection, and antiviral drugs that selectively interfere with viral replication.


Vaccination is a cheap and effective way of preventing infections by viruses. Vaccines were used to prevent viral infections long before the discovery of the actual viruses. Their use has resulted in a dramatic decline in morbidity (illness) and mortality (death) associated with viral infections such as polio, measles, mumps and rubella. [212] Smallpox infections have been eradicated. [213] Vaccines are available to prevent over thirteen viral infections of humans, [214] and more are used to prevent viral infections of animals. [215] Vaccines can consist of live-attenuated or killed viruses, or viral proteins (antigens). [216] Live vaccines contain weakened forms of the virus, which do not cause the disease but, nonetheless, confer immunity. Such viruses are called attenuated. Live vaccines can be dangerous when given to people with a weak immunity (who are described as immunocompromised), because in these people, the weakened virus can cause the original disease. [217] Biotechnology and genetic engineering techniques are used to produce subunit vaccines. These vaccines use only the capsid proteins of the virus. Hepatitis B vaccine is an example of this type of vaccine. [218] Subunit vaccines are safe for immunocompromised patients because they cannot cause the disease. [219] The yellow fever virus vaccine, a live-attenuated strain called 17D, is probably the safest and most effective vaccine ever generated. [220]

Antiviral drugs

Antiviral drugs are often nucleoside analogues (fake DNA building-blocks), which viruses mistakenly incorporate into their genomes during replication. The life-cycle of the virus is then halted because the newly synthesised DNA is inactive. This is because these analogues lack the hydroxyl groups, which, along with phosphorus atoms, link together to form the strong "backbone" of the DNA molecule. This is called DNA chain termination. [221] Examples of nucleoside analogues are aciclovir for Herpes simplex virus infections and lamivudine for HIV and hepatitis B virus infections. Aciclovir is one of the oldest and most frequently prescribed antiviral drugs. [222] Other antiviral drugs in use target different stages of the viral life cycle. HIV is dependent on a proteolytic enzyme called the HIV-1 protease for it to become fully infectious. There is a large class of drugs called protease inhibitors that inactivate this enzyme. [223]

Hepatitis C is caused by an RNA virus. In 80% of people infected, the disease is chronic, and without treatment, they are infected for the remainder of their lives. There is now an effective treatment that uses the nucleoside analogue drug ribavirin combined with interferon. [224] The treatment of chronic carriers of the hepatitis B virus by using a similar strategy using lamivudine has been developed. [225]

Viruses infect all cellular life and, although viruses occur universally, each cellular species has its own specific range that often infects only that species. [226] Some viruses, called satellites, can replicate only within cells that have already been infected by another virus. [61]

Animal viruses

Viruses are important pathogens of livestock. Diseases such as foot-and-mouth disease and bluetongue are caused by viruses. [227] Companion animals such as cats, dogs, and horses, if not vaccinated, are susceptible to serious viral infections. Canine parvovirus is caused by a small DNA virus and infections are often fatal in pups. [228] Like all invertebrates, the honey bee is susceptible to many viral infections. [229] Most viruses co-exist harmlessly in their host and cause no signs or symptoms of disease. [4]

Plant viruses

There are many types of plant viruses, but often they cause only a loss of yield, and it is not economically viable to try to control them. Plant viruses are often spread from plant to plant by organisms, known as vectors. These are usually insects, but some fungi, nematode worms, and single-celled organisms are vectors. When control of plant virus infections is considered economical, for perennial fruits, for example, efforts are concentrated on killing the vectors and removing alternate hosts such as weeds. [230] Plant viruses cannot infect humans and other animals because they can reproduce only in living plant cells. [231]

Originally from Peru, the potato has become a staple crop worldwide. [232] The potato virus Y causes disease in potatoes and related species including tomatoes and peppers. In the 1980s, this virus acquired economical importance when it proved difficult to control in seed potato crops. Transmitted by aphids, this virus can reduce crop yields by up to 80 per cent, causing significant losses to potato yields. [233]

Plants have elaborate and effective defence mechanisms against viruses. One of the most effective is the presence of so-called resistance (R) genes. Each R gene confers resistance to a particular virus by triggering localised areas of cell death around the infected cell, which can often be seen with the unaided eye as large spots. This stops the infection from spreading. [234] RNA interference is also an effective defence in plants. [235] When they are infected, plants often produce natural disinfectants that kill viruses, such as salicylic acid, nitric oxide, and reactive oxygen molecules. [236]

Plant virus particles or virus-like particles (VLPs) have applications in both biotechnology and nanotechnology. The capsids of most plant viruses are simple and robust structures and can be produced in large quantities either by the infection of plants or by expression in a variety of heterologous systems. Plant virus particles can be modified genetically and chemically to encapsulate foreign material and can be incorporated into supramolecular structures for use in biotechnology. [237]

Bacterial viruses

Bacteriophages are a common and diverse group of viruses and are the most abundant biological entity in aquatic environments—there are up to ten times more of these viruses in the oceans than there are bacteria, [238] reaching levels of 250,000,000 bacteriophages per millilitre of seawater. [239] These viruses infect specific bacteria by binding to surface receptor molecules and then entering the cell. Within a short amount of time, in some cases, just minutes, bacterial polymerase starts translating viral mRNA into protein. These proteins go on to become either new virions within the cell, helper proteins, which help assembly of new virions, or proteins involved in cell lysis. Viral enzymes aid in the breakdown of the cell membrane, and, in the case of the T4 phage, in just over twenty minutes after injection over three hundred phages could be released. [240]

The major way bacteria defend themselves from bacteriophages is by producing enzymes that destroy foreign DNA. These enzymes, called restriction endonucleases, cut up the viral DNA that bacteriophages inject into bacterial cells. [241] Bacteria also contain a system that uses CRISPR sequences to retain fragments of the genomes of viruses that the bacteria have come into contact with in the past, which allows them to block the virus's replication through a form of RNA interference. [242] [243] This genetic system provides bacteria with acquired immunity to infection. [244]

Archaeal viruses

Some viruses replicate within archaea: these are DNA viruses with unusual and sometimes unique shapes. [7] [92] These viruses have been studied in most detail in the thermophilic archaea, particularly the orders Sulfolobales and Thermoproteales. [245] Defences against these viruses involve RNA interference from repetitive DNA sequences within archaean genomes that are related to the genes of the viruses. [246] [247] Most archaea have CRISPR–Cas systems as an adaptive defence against viruses. These enable archaea to retain sections of viral DNA, which are then used to target and eliminate subsequent infections by the virus using a process similar to RNA interference. [248]

Viruses are the most abundant biological entity in aquatic environments. [2] There are about ten million of them in a teaspoon of seawater. [249] Most of these viruses are bacteriophages infecting heterotrophic bacteria and cyanophages infecting cyanobacteria and they are essential to the regulation of saltwater and freshwater ecosystems. [250] Bacteriophages are harmless to plants and animals, and are essential to the regulation of marine and freshwater ecosystems [251] are important mortality agents of phytoplankton, the base of the foodchain in aquatic environments. [252] They infect and destroy bacteria in aquatic microbial communities, and are one of the most important mechanisms of recycling carbon and nutrient cycling in marine environments. The organic molecules released from the dead bacterial cells stimulate fresh bacterial and algal growth, in a process known as the viral shunt. [253] In particular, lysis of bacteria by viruses has been shown to enhance nitrogen cycling and stimulate phytoplankton growth. [254] Viral activity may also affect the biological pump, the process whereby carbon is sequestered in the deep ocean. [255]

Microorganisms constitute more than 90% of the biomass in the sea. It is estimated that viruses kill approximately 20% of this biomass each day and that there are 10 to 15 times as many viruses in the oceans as there are bacteria and archaea. [256] Viruses are also major agents responsible for the destruction of phytoplankton including harmful algal blooms, [257] The number of viruses in the oceans decreases further offshore and deeper into the water, where there are fewer host organisms. [255]

In January 2018, scientists reported that 800 million viruses, mainly of marine origin, are deposited daily from the Earth 's atmosphere onto every square meter of the planet's surface, as the result of a global atmospheric stream of viruses, circulating above the weather system but below the altitude of usual airline travel, distributing viruses around the planet. [258] [259]

Like any organism, marine mammals are susceptible to viral infections. In 1988 and 2002, thousands of harbour seals were killed in Europe by phocine distemper virus. [260] Many other viruses, including caliciviruses, herpesviruses, adenoviruses and parvoviruses, circulate in marine mammal populations. [255]

Viruses are an important natural means of transferring genes between different species, which increases genetic diversity and drives evolution. [9] [261] It is thought that viruses played a central role in early evolution, before the diversification of the last universal common ancestor into bacteria, archaea and eukaryotes. [262] Viruses are still one of the largest reservoirs of unexplored genetic diversity on Earth. [255]

Life sciences and medicine

Viruses are important to the study of molecular and cell biology as they provide simple systems that can be used to manipulate and investigate the functions of cells. [263] The study and use of viruses have provided valuable information about aspects of cell biology. [264] For example, viruses have been useful in the study of genetics and helped our understanding of the basic mechanisms of molecular genetics, such as DNA replication, transcription, RNA processing, translation, protein transport, and immunology.

Geneticists often use viruses as vectors to introduce genes into cells that they are studying. This is useful for making the cell produce a foreign substance, or to study the effect of introducing a new gene into the genome. Similarly, virotherapy uses viruses as vectors to treat various diseases, as they can specifically target cells and DNA. It shows promising use in the treatment of cancer and in gene therapy. Eastern European scientists have used phage therapy as an alternative to antibiotics for some time, and interest in this approach is increasing, because of the high level of antibiotic resistance now found in some pathogenic bacteria. [265] The expression of heterologous proteins by viruses is the basis of several manufacturing processes that are currently being used for the production of various proteins such as vaccine antigens and antibodies. Industrial processes have been recently developed using viral vectors and several pharmaceutical proteins are currently in pre-clinical and clinical trials. [266]


Virotherapy involves the use of genetically modified viruses to treat diseases. [267] Viruses have been modified by scientists to reproduce in cancer cells and destroy them but not infect healthy cells. Talimogene laherparepvec (T-VEC), for example, is a modified herpes simplex virus that has had a gene, which is required for viruses to replicate in healthy cells, deleted and replaced with a human gene (GM-CSF) that stimulates immunity. When this virus infects cancer cells, it destroys them and in doing so the presence the GM-CSF gene attracts dendritic cells from the surrounding tissues of the body. The dendritic cells process the dead cancer cells and present components of them to other cells of the immune system. [268] Having completed successful clinical trials, the virus gained approval for the treatment of melanoma in late 2015. [269] Viruses that have been reprogrammed to kill cancer cells are called oncolytic viruses. [270]

Materials science and nanotechnology

Current trends in nanotechnology promise to make much more versatile use of viruses. [271] From the viewpoint of a materials scientist, viruses can be regarded as organic nanoparticles. Their surface carries specific tools that enable them to cross the barriers of their host cells. The size and shape of viruses and the number and nature of the functional groups on their surface are precisely defined. As such, viruses are commonly used in materials science as scaffolds for covalently linked surface modifications. A particular quality of viruses is that they can be tailored by directed evolution. The powerful techniques developed by life sciences are becoming the basis of engineering approaches towards nanomaterials, opening a wide range of applications far beyond biology and medicine. [272]

Because of their size, shape, and well-defined chemical structures, viruses have been used as templates for organising materials on the nanoscale. Recent examples include work at the Naval Research Laboratory in Washington, D.C., using Cowpea mosaic virus (CPMV) particles to amplify signals in DNA microarray based sensors. In this application, the virus particles separate the fluorescent dyes used for signalling to prevent the formation of non-fluorescent dimers that act as quenchers. [273] Another example is the use of CPMV as a nanoscale breadboard for molecular electronics. [274]

Synthetic viruses

Many viruses can be synthesised de novo ("from scratch") and the first synthetic virus was created in 2002. [275] Although somewhat of a misconception, it is not the actual virus that is synthesised, but rather its DNA genome (in case of a DNA virus), or a cDNA copy of its genome (in case of RNA viruses). For many virus families the naked synthetic DNA or RNA (once enzymatically converted back from the synthetic cDNA) is infectious when introduced into a cell. That is, they contain all the necessary information to produce new viruses. This technology is now being used to investigate novel vaccine strategies. [276] The ability to synthesise viruses has far-reaching consequences, since viruses can no longer be regarded as extinct, as long as the information of their genome sequence is known and permissive cells are available. As of February 2021 [update] , the full-length genome sequences of 10462 different viruses, including smallpox, are publicly available in an online database maintained by the National Institutes of Health. [277]


The ability of viruses to cause devastating epidemics in human societies has led to the concern that viruses could be weaponised for biological warfare. Further concern was raised by the successful recreation of the infamous 1918 influenza virus in a laboratory. [278] The smallpox virus devastated numerous societies throughout history before its eradication. There are only two centres in the world authorised by the WHO to keep stocks of smallpox virus: the State Research Center of Virology and Biotechnology VECTOR in Russia and the Centers for Disease Control and Prevention in the United States. [279] It may be used as a weapon, [279] as the vaccine for smallpox sometimes had severe side-effects, it is no longer used routinely in any country. Thus, much of the modern human population has almost no established resistance to smallpox and would be vulnerable to the virus. [279]


  1. ^ Wu KJ (15 April 2020). "There are more viruses than stars in the universe. Why do only some infect us? – More than a quadrillion quadrillion individual viruses exist on Earth, but most are not poised to hop into humans. Can we find the ones that are?". National Geographic Society . Retrieved 18 May 2020 .
  2. ^ abc
  3. Koonin EV, Senkevich TG, Dolja VV (September 2006). "The ancient Virus World and evolution of cells". Biology Direct. 1 (1): 29. doi:10.1186/1745-6150-1-29. PMC1594570 . PMID16984643.
  4. ^
  5. Zimmer C (26 February 2021). "The Secret Life of a Coronavirus - An oily, 100-nanometer-wide bubble of genes has killed more than two million people and reshaped the world. Scientists don't quite know what to make of it" . Retrieved 28 February 2021 .
  6. ^ abc Dimmock p. 4
  7. ^ ab
  8. "Virus Taxonomy: 2020 Release". International Committee on Taxonomy of Viruses . Retrieved 21 May 2021 .
  9. ^ ab
  10. Breitbart M, Rohwer F (June 2005). "Here a virus, there a virus, everywhere the same virus?". Trends in Microbiology. 13 (6): 278–84. doi:10.1016/j.tim.2005.04.003. PMID15936660.
  11. ^ ab
  12. Lawrence CM, Menon S, Eilers BJ, Bothner B, Khayat R, Douglas T, Young MJ (May 2009). "Structural and functional studies of archaeal viruses". The Journal of Biological Chemistry. 284 (19): 12599–603. doi:10.1074/jbc.R800078200. PMC2675988 . PMID19158076.
  13. ^
  14. Edwards RA, Rohwer F (June 2005). "Viral metagenomics". Nature Reviews. Microbiology. 3 (6): 504–10. doi:10.1038/nrmicro1163. PMID15886693. S2CID8059643.
  15. ^ ab
  16. Canchaya C, Fournous G, Chibani-Chennoufi S, Dillmann ML, Brüssow H (August 2003). "Phage as agents of lateral gene transfer". Current Opinion in Microbiology. 6 (4): 417–24. doi:10.1016/S1369-5274(03)00086-9. PMID12941415.
  17. ^ ab
  18. Rybicki EP (1990). "The classification of organisms at the edge of life, or problems with virus systematics". South African Journal of Science. 86: 182–86.
  19. ^ ab
  20. Koonin EV, Starokadomskyy P (October 2016). "Are viruses alive? The replicator paradigm sheds decisive light on an old but misguided question". Studies in History and Philosophy of Biological and Biomedical Sciences. 59: 125–34. doi:10.1016/j.shpsc.2016.02.016. PMC5406846 . PMID26965225.
  21. ^
  22. Robilotti E, Deresinski S, Pinsky BA (January 2015). "Norovirus". Clinical Microbiology Reviews. 28 (1): 134–64. doi:10.1128/CMR.00075-14. PMC4284304 . PMID25567225.
  23. ^ Shors pp. 123–124
  24. ^
  25. "Virus, n.". OED Online. Oxford University Press. March 2015.
  26. ^ ab
  27. Harper D (2011). "virus". The Online Etymology Dictionary . Retrieved 19 December 2014 .
  28. ^
  29. "Virulent, adj.". OED Online. Oxford University Press. March 2015.
  30. ^
  31. Harper D (2011). "virulent". The Online Etymology Dictionary . Retrieved 19 December 2014 .
  32. ^
  33. Buschard K, Thon R (2003). "Diabetic Animal Models". In Hau J, Van Hoosier Jr GL (eds.). Handbook of Laboratory Animal Science. Animal Models. II (Second ed.). CRC Press. pp. 163, 166.
  34. ^ William T. Stearn: Botanical Latin. History, Grammar, Syntax, Terminology and Vocabulary. David & Charles, third edition, 1983. Quote: "Virus: virus (s.n. II), gen. sing. viri, nom. pl. vira, gen. pl. vīrorum (to be distinguished from virorum, of men)."
  35. ^
  36. Harper D (2011). "viral". The Online Etymology Dictionary . Retrieved 19 December 2014 .
  37. ^
  38. Harper D (2011). "virion". The Online Etymology Dictionary . Retrieved 19 December 2014 .
  39. ^
  40. Casjens S (2010). Mahy BW, Van Regenmortel MH (eds.). Desk Encyclopedia of General Virology. Boston: Academic Press. p. 167. ISBN978-0-12-375146-1 .
  41. ^
  42. Bordenave G (May 2003). "Louis Pasteur (1822-1895)". Microbes and Infection. 5 (6): 553–60. doi:10.1016/S1286-4579(03)00075-3. PMID12758285.
  43. ^ Shors pp. 74, 827
  44. ^ ab Collier p. 3
  45. ^ Dimmock pp. 4–5
  46. ^
  47. Fenner F (2009). Mahy BW, Van Regenmortal MH (eds.). Desk Encyclopedia of General Virology (1 ed.). Oxford: Academic Press. p. 15. ISBN978-0-12-375146-1 .
  48. ^ Shors p. 827
  49. ^
  50. D'Herelle F (September 2007). "On an invisible microbe antagonistic toward dysenteric bacilli: brief note by Mr. F. D'Herelle, presented by Mr. Roux. 1917". Research in Microbiology. 158 (7): 553–54. doi:10.1016/j.resmic.2007.07.005. PMID17855060.
  51. ^
  52. Domingo-Calap P, Georgel P, Bahram S (March 2016). "Back to the future: bacteriophages as promising therapeutic tools". HLA. 87 (3): 133–40. doi:10.1111/tan.12742. PMID26891965. S2CID29223662.
  53. ^
  54. Steinhardt E, Israeli C, Lambert RA (1913). "Studies on the cultivation of the virus of vaccinia". The Journal of Infectious Diseases. 13 (2): 294–300. doi:10.1093/infdis/13.2.294.
  55. ^ Collier p. 4
  56. ^
  57. Goodpasture EW, Woodruff AM, Buddingh GJ (October 1931). "The cultivation of vaccine and other viruses in the chorioallantoic membrane of chick embryos". Science. 74 (1919): 371–72. Bibcode:1931Sci. 74..371G. doi:10.1126/science.74.1919.371. PMID17810781.
  58. ^
  59. Thomas Huckle Weller (2004). Growing Pathogens in Tissue Cultures: Fifty Years in Academic Tropical Medicine, Pediatrics, and Virology. Boston Medical Library. p. 57. ISBN978-0-88135-380-8 .
  60. ^
  61. Rosen FS (October 2004). "Isolation of poliovirus--John Enders and the Nobel Prize". The New England Journal of Medicine. 351 (15): 1481–83. doi:10.1056/NEJMp048202. PMID15470207.
  62. ^
  63. Frängsmyr T, Ekspång G, eds. (1993). Nobel Lectures, Physics 1981–1990. Singapore: World Scientific Publishing Co. F.
    • In 1887, Buist visualised one of the largest, Vaccinia virus, by optical microscopy after staining it. Vaccinia was not known to be a virus at that time. (Buist J.B. Vaccinia and Variola: a study of their life history Churchill, London)
  64. ^
  65. Stanley WM, Loring HS (January 1936). "The Isolation of Crystalline Tobacco Mosaic Virus Protein From Diseased Tomato Plants". Science. 83 (2143): 85. Bibcode:1936Sci. 83. 85S. doi:10.1126/science.83.2143.85. PMID17756690.
  66. ^
  67. Stanley WM, Lauffer MA (April 1939). "Disintegration of Tobacco Mosaic Virus in Urea Solutions". Science. 89 (2311): 345–47. Bibcode:1939Sci. 89..345S. doi:10.1126/science.89.2311.345. PMID17788438.
  68. ^
  69. Creager AN, Morgan GJ (June 2008). "After the double helix: Rosalind Franklin's research on Tobacco mosaic virus". Isis an International Review Devoted to the History of Science and Its Cultural Influences. 99 (2): 239–72. doi:10.1086/588626. PMID18702397. S2CID25741967.
  70. ^ Dimmock p. 12
  71. ^
  72. Norrby E (2008). "Nobel Prizes and the emerging virus concept". Archives of Virology. 153 (6): 1109–23. doi:10.1007/s00705-008-0088-8. PMID18446425. S2CID10595263.
  73. ^ Collier p. 745
  74. ^ ab
  75. Temin HM, Baltimore D (1972). "RNA-directed DNA synthesis and RNA tumor viruses". Advances in Virus Research. 17: 129–86. doi:10.1016/S0065-3527(08)60749-6. ISBN9780120398171 . PMID4348509.
  76. ^
  77. Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, et al. (May 1983). "Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS)". Science. 220 (4599): 868–71. Bibcode:1983Sci. 220..868B. doi:10.1126/science.6189183. PMID6189183.
  78. ^
  79. Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M (April 1989). "Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome". Science. 244 (4902): 359–62. Bibcode:1989Sci. 244..359C. CiteSeerX10.1.1.469.3592 . doi:10.1126/science.2523562. PMID2523562.
  80. ^
  81. Houghton M (November 2009). "The long and winding road leading to the identification of the hepatitis C virus". Journal of Hepatology. 51 (5): 939–48. doi: 10.1016/j.jhep.2009.08.004 . PMID19781804.
  82. ^
  83. Iyer LM, Balaji S, Koonin EV, Aravind L (April 2006). "Evolutionary genomics of nucleo-cytoplasmic large DNA viruses". Virus Research. 117 (1): 156–84. doi:10.1016/j.virusres.2006.01.009. PMID16494962.
  84. ^ ab
  85. Sanjuán R, Nebot MR, Chirico N, Mansky LM, Belshaw R (October 2010). "Viral mutation rates". Journal of Virology. 84 (19): 9733–48. doi:10.1128/JVI.00694-10. PMC2937809 . PMID20660197.
  86. ^ Shors pp. 14–16
  87. ^ Collier pp. 11–21
  88. ^ ab Dimmock p. 16
  89. ^ Collier p. 11
  90. ^ abcd
  91. Mahy WJ, Regenmortel MH, eds. (2009). Desk Encyclopedia of General Virology. Oxford: Academic Press. p. 24. ISBN978-0-12-375146-1 .
  92. ^ Shors p. 810
  93. ^
  94. McClintock B (June 1950). "The origin and behavior of mutable loci in maize". Proceedings of the National Academy of Sciences of the United States of America. 36 (6): 344–55. Bibcode:1950PNAS. 36..344M. doi:10.1073/pnas.36.6.344. PMC1063197 . PMID15430309.
  95. ^ Collier pp. 11–12
  96. ^ Dimmock p. 55
  97. ^ Shors pp. 791
  98. ^
  99. Tsagris EM, Martínez de Alba AE, Gozmanova M, Kalantidis K (November 2008). "Viroids". Cellular Microbiology. 10 (11): 2168–79. doi: 10.1111/j.1462-5822.2008.01231.x . PMID18764915. S2CID221581424.
  100. ^ Shors pp. 460
  101. ^ ab
  102. La Scola B, Desnues C, Pagnier I, Robert C, Barrassi L, Fournous G, et al. (September 2008). "The virophage as a unique parasite of the giant mimivirus". Nature. 455 (7209): 100–04. Bibcode:2008Natur.455..100L. doi:10.1038/nature07218. PMID18690211. S2CID4422249.
  103. ^ Collier p. 777
  104. ^ Dimmock pp. 55–57
  105. ^ ab
  106. Mahy WJ, Van Regenmortel MH, eds. (2009). Desk Encyclopedia of General Virology. Oxford: Academic Press. p. 28. ISBN978-0-12-375146-1 .
  107. ^ ab
  108. Mahy WJ, Regenmortel MH, eds. (2009). Desk Encyclopedia of General Virology. Oxford: Academic Press. p. 26. ISBN978-0-12-375146-1 .
  109. ^ Dimmock pp. 15–16
  110. ^
  111. Holmes EC (October 2007). "Viral evolution in the genomic age". PLOS Biology. 5 (10): e278. doi:10.1371/journal.pbio.0050278. PMC1994994 . PMID17914905.
  112. ^
  113. Wimmer E, Mueller S, Tumpey TM, Taubenberger JK (December 2009). "Synthetic viruses: a new opportunity to understand and prevent viral disease". Nature Biotechnology. 27 (12): 1163–72. doi:10.1038/nbt.1593. PMC2819212 . PMID20010599.
  114. ^
  115. Horn M (2008). "Chlamydiae as symbionts in eukaryotes". Annual Review of Microbiology. 62: 113–31. doi:10.1146/annurev.micro.62.081307.162818. PMID18473699.
  116. ^
  117. Ammerman NC, Beier-Sexton M, Azad AF (November 2008). "Laboratory maintenance of Rickettsia rickettsii". Current Protocols in Microbiology. 11 (1): 3A.5.1–3A.5.21. doi:10.1002/9780471729259.mc03a05s11. ISBN978-0471729259 . PMC2725428 . PMID19016440.
  118. ^ ab Collier pp. 33–55
  119. ^ Collier pp. 33–37
  120. ^
  121. Kiselev NA, Sherman MB, Tsuprun VL (1990). "Negative staining of proteins". Electron Microscopy Reviews. 3 (1): 43–72. doi:10.1016/0892-0354(90)90013-I. PMID1715774.
  122. ^ Collier p. 40
  123. ^
  124. Caspar DL, Klug A (1962). "Physical principles in the construction of regular viruses". Cold Spring Harbor Symposia on Quantitative Biology. 27: 1–24. doi:10.1101/sqb.1962.027.001.005. PMID14019094.
  125. ^
  126. Crick FH, Watson JD (March 1956). "Structure of small viruses". Nature. 177 (4506): 473–75. Bibcode:1956Natur.177..473C. doi:10.1038/177473a0. PMID13309339. S2CID5740221.
  127. ^
  128. Falvo MR, Washburn S, Superfine R, Finch M, Brooks FP, Chi V, Taylor RM (March 1997). "Manipulation of individual viruses: friction and mechanical properties". Biophysical Journal. 72 (3): 1396–403. Bibcode:1997BpJ. 72.1396F. doi:10.1016/S0006-3495(97)78786-1. PMC1184522 . PMID9138585.
  129. ^
  130. Kuznetsov YG, Malkin AJ, Lucas RW, Plomp M, McPherson A (September 2001). "Imaging of viruses by atomic force microscopy". The Journal of General Virology. 82 (Pt 9): 2025–34. doi: 10.1099/0022-1317-82-9-2025 . PMID11514711.
  131. ^ Collier p. 37
  132. ^
  133. Straus SK, Bo HE (2018). "Filamentous Bacteriophage Proteins and Assembly". Sub-Cellular Biochemistry. 88: 261–279. doi:10.1007/978-981-10-8456-0_12. ISBN978-981-10-8455-3 . PMID29900501.
  134. ^ Collier pp. 40, 42
  135. ^
  136. Wilson DP (2016). "Protruding Features of Viral Capsids Are Clustered on Icosahedral Great Circles". PLOS ONE. 11 (4): e0152319. Bibcode:2016PLoSO..1152319W. doi:10.1371/journal.pone.0152319. PMC4821576 . PMID27045511.
  137. ^
  138. Casens S (2009). Desk Encyclopedia of General Virology. Boston: Academic Press. pp. 167–74. ISBN978-0-12-375146-1 .
  139. ^
  140. Dhama K, Khan S, Tiwari R, Sircar S, Bhat S, Malik YS, Singh KP, Chaicumpa W, Bonilla-Aldana DK, Rodriguez-Morales AJ (September 2020). "Coronavirus Disease 2019-COVID-19". Clinical Microbiology Reviews. 33 (4). doi:10.1128/CMR.00028-20. PMC7405836 . PMID32580969.
  141. ^ Collier pp. 42–43
  142. ^
  143. Rossmann MG, Mesyanzhinov VV, Arisaka F, Leiman PG (April 2004). "The bacteriophage T4 DNA injection machine". Current Opinion in Structural Biology. 14 (2): 171–80. doi:10.1016/ PMID15093831.
  144. ^
  145. Long GW, Nobel J, Murphy FA, Herrmann KL, Lourie B (September 1970). "Experience with electron microscopy in the differential diagnosis of smallpox". Applied Microbiology. 20 (3): 497–504. doi:10.1128/AEM.20.3.497-504.1970. PMC376966 . PMID4322005.
  146. ^
  147. Suzan-Monti M, La Scola B, Raoult D (April 2006). "Genomic and evolutionary aspects of Mimivirus". Virus Research. 117 (1): 145–55. doi:10.1016/j.virusres.2005.07.011. PMID16181700.
  148. ^
  149. Arslan D, Legendre M, Seltzer V, Abergel C, Claverie JM (October 2011). "Distant Mimivirus relative with a larger genome highlights the fundamental features of Megaviridae". Proceedings of the National Academy of Sciences of the United States of America. 108 (42): 17486–91. Bibcode:2011PNAS..10817486A. doi:10.1073/pnas.1110889108. PMC3198346 . PMID21987820.
  150. ^ ab
  151. Philippe N, Legendre M, Doutre G, Couté Y, Poirot O, Lescot M, et al. (July 2013). "Pandoraviruses: amoeba viruses with genomes up to 2.5 Mb reaching that of parasitic eukaryotes" (PDF) . Science. 341 (6143): 281–86. Bibcode:2013Sci. 341..281P. doi:10.1126/science.1239181. PMID23869018. S2CID16877147.
  152. ^
  153. Brandes N, Linial M (April 2019). "Giant Viruses-Big Surprises". Viruses. 11 (5): 404. doi:10.3390/v11050404. PMC6563228 . PMID31052218.
  154. ^ ab
  155. Prangishvili D, Forterre P, Garrett RA (November 2006). "Viruses of the Archaea: a unifying view". Nature Reviews. Microbiology. 4 (11): 837–48. doi:10.1038/nrmicro1527. PMID17041631. S2CID9915859.
  156. ^ ab Dimmock p. 49
  157. ^
  158. "NCBI Viral Genome database". . Retrieved 15 January 2017 .
  159. ^
  160. Pennisi E (March 2011). "Microbiology. Going viral: exploring the role of viruses in our bodies". Science. 331 (6024): 1513. Bibcode:2011Sci. 331.1513P. doi:10.1126/science.331.6024.1513. PMID21436418.
  161. ^
  162. Shi M, Lin XD, Tian JH, Chen LJ, Chen X, Li CX, et al. (December 2016). "Redefining the invertebrate RNA virosphere". Nature. 540 (7634): 539–43. Bibcode:2016Natur.540..539S. doi:10.1038/nature20167. PMID27880757. S2CID1198891.
  163. ^ abc Collier pp. 96–99
  164. ^
  165. Saunders VA, Carter J (2007). Virology: principles and applications. Chichester: John Wiley & Sons. p. 72. ISBN978-0-470-02387-7 .
  166. ^
  167. Belyi VA, Levine AJ, Skalka AM (December 2010). "Sequences from ancestral single-stranded DNA viruses in vertebrate genomes: the parvoviridae and circoviridae are more than 40 to 50 million years old". Journal of Virology. 84 (23): 12458–62. doi:10.1128/JVI.01789-10. PMC2976387 . PMID20861255.
  168. ^
  169. Brandes N, Linial M (May 2016). "Gene overlapping and size constraints in the viral world". Biology Direct. 11 (1): 26. doi:10.1186/s13062-016-0128-3. PMC4875738 . PMID27209091.
  170. ^
  171. Pressing J, Reanney DC (1984). "Divided genomes and intrinsic noise". Journal of Molecular Evolution. 20 (2): 135–46. Bibcode:1984JMolE..20..135P. doi:10.1007/BF02257374. PMC7087551 . PMID6433032.
  172. ^
  173. Duffy S, Holmes EC (June 2009). "Validation of high rates of nucleotide substitution in geminiviruses: phylogenetic evidence from East African cassava mosaic viruses". The Journal of General Virology. 90 (Pt 6): 1539–47. doi:10.1099/vir.0.009266-0. PMC4091138 . PMID19264617.
  174. ^
  175. Sandbulte MR, Westgeest KB, Gao J, Xu X, Klimov AI, Russell CA, et al. (December 2011). "Discordant antigenic drift of neuraminidase and hemagglutinin in H1N1 and H3N2 influenza viruses". Proceedings of the National Academy of Sciences of the United States of America. 108 (51): 20748–53. Bibcode:2011PNAS..10820748S. doi:10.1073/pnas.1113801108. PMC3251064 . PMID22143798.
  176. ^
  177. Moss RB, Davey RT, Steigbigel RT, Fang F (June 2010). "Targeting pandemic influenza: a primer on influenza antivirals and drug resistance". The Journal of Antimicrobial Chemotherapy. 65 (6): 1086–93. doi: 10.1093/jac/dkq100 . PMID20375034.
  178. ^
  179. Hampson AW, Mackenzie JS (November 2006). "The influenza viruses". The Medical Journal of Australia. 185 (S10): S39–43. doi:10.5694/j.1326-5377.2006.tb00705.x. PMID17115950. S2CID17069567.
  180. ^
  181. Metzner KJ (December 2006). "Detection and significance of minority quasispecies of drug-resistant HIV-1". Journal of HIV Therapy. 11 (4): 74–81. PMID17578210.
  182. ^ Goudsmit, Jaap. Viral Sex. Oxford Univ Press, 1998. 978-0-19-512496-5, 0-19-512496-0
  183. ^
  184. Worobey M, Holmes EC (October 1999). "Evolutionary aspects of recombination in RNA viruses". The Journal of General Virology. 80 (10): 2535–43. doi: 10.1099/0022-1317-80-10-2535 . PMID10573145.
  185. ^
  186. Lukashev AN (2005). "Role of recombination in evolution of enteroviruses". Reviews in Medical Virology. 15 (3): 157–67. doi:10.1002/rmv.457. PMID15578739. S2CID26000112.
  187. ^
  188. Umene K (July 1999). "Mechanism and application of genetic recombination in herpesviruses". Reviews in Medical Virology. 9 (3): 171–82. doi:10.1002/(SICI)1099-1654(199907/09)9:3<171::AID-RMV243>3.0.CO2-A. PMID10479778.
  189. ^
  190. Freed EO (August 2015). "HIV-1 assembly, release and maturation". Nature Reviews. Microbiology. 13 (8): 484–96. doi:10.1038/nrmicro3490. PMC6936268 . PMID26119571.
  191. ^
  192. Yin J, Redovich J (June 2018). "Kinetic Modeling of Virus Growth in Cells". Microbiology and Molecular Biology Reviews. 82 (2). doi:10.1128/MMBR.00066-17. PMC5968458 . PMID29592895.
  193. ^ Collier pp. 75–91
  194. ^
  195. Más V, Melero JA (2013). "Entry of enveloped viruses into host cells: membrane fusion". Structure and Physics of Viruses. Subcellular Biochemistry. 68. pp. 467–87. doi:10.1007/978-94-007-6552-8_16. ISBN978-94-007-6551-1 . PMC7121288 . PMID23737062.
  196. ^ Dimmock p. 70
  197. ^
  198. Boevink P, Oparka KJ (August 2005). "Virus-host interactions during movement processes". Plant Physiology. 138 (4): 1815–21. doi:10.1104/pp.105.066761. PMC1183373 . PMID16172094.
  199. ^ Dimmock p. 71
  200. ^
  201. Blaas D (May 2016). "Viral entry pathways: the example of common cold viruses". Wiener Medizinische Wochenschrift. 166 (7–8): 211–26. doi:10.1007/s10354-016-0461-2. PMC4871925 . PMID27174165.
  202. ^
  203. Isomura H, Stinski MF (February 2013). "Coordination of late gene transcription of human cytomegalovirus with viral DNA synthesis: recombinant viruses as potential therapeutic vaccine candidates". Expert Opinion on Therapeutic Targets. 17 (2): 157–66. doi:10.1517/14728222.2013.740460. PMID23231449. S2CID11448687.
  204. ^
  205. Barman S, Ali A, Hui EK, Adhikary L, Nayak DP (September 2001). "Transport of viral proteins to the apical membranes and interaction of matrix protein with glycoproteins in the assembly of influenza viruses". Virus Research. 77 (1): 61–69. doi:10.1016/S0168-1702(01)00266-0. PMID11451488.
  206. ^ Shors pp. 836
  207. ^ Dimmock, Chapter 15, Mechanisms in virus latency, pp. 243–59
  208. ^ Dimmock 185–87
  209. ^ Shors p. 118 Collier p. 78
  210. ^ Collier p. 79
  211. ^
  212. Staginnus C, Richert-Pöggeler KR (October 2006). "Endogenous pararetroviruses: two-faced travelers in the plant genome". Trends in Plant Science. 11 (10): 485–91. doi:10.1016/j.tplants.2006.08.008. PMID16949329.
  213. ^ Collier pp. 88–89
  214. ^ Collier pp. 115–46
  215. ^ Collier p. 115
  216. ^
  217. Roulston A, Marcellus RC, Branton PE (1999). "Viruses and apoptosis". Annual Review of Microbiology. 53: 577–628. doi:10.1146/annurev.micro.53.1.577. PMID10547702.
  218. ^
  219. Alwine JC (2008). "Modulation of host cell stress responses by human cytomegalovirus". Current Topics in Microbiology and Immunology. 325: 263–79. doi:10.1007/978-3-540-77349-8_15. ISBN978-3-540-77348-1 . PMID18637511.
  220. ^
  221. Barozzi P, Potenza L, Riva G, Vallerini D, Quadrelli C, Bosco R, et al. (December 2007). "B cells and herpesviruses: a model of lymphoproliferation". Autoimmunity Reviews. 7 (2): 132–36. doi:10.1016/j.autrev.2007.02.018. PMID18035323.
  222. ^
  223. Subramanya D, Grivas PD (November 2008). "HPV and cervical cancer: updates on an established relationship". Postgraduate Medicine. 120 (4): 7–13. doi:10.3810/pgm.2008.11.1928. PMID19020360. S2CID1399003.
  224. ^
  225. Sinclair J (March 2008). "Human cytomegalovirus: Latency and reactivation in the myeloid lineage". Journal of Clinical Virology. 41 (3): 180–85. doi:10.1016/j.jcv.2007.11.014. PMID18164651.
  226. ^
  227. Jordan MC, Jordan GW, Stevens JG, Miller G (June 1984). "Latent herpesviruses of humans". Annals of Internal Medicine. 100 (6): 866–80. doi:10.7326/0003-4819-100-6-866. PMID6326635.
  228. ^
  229. Sissons JG, Bain M, Wills MR (February 2002). "Latency and reactivation of human cytomegalovirus". The Journal of Infection. 44 (2): 73–77. doi:10.1053/jinf.2001.0948. PMID12076064.
  230. ^
  231. Crawford DH (2011). Viruses: A Very Short Introduction. Oxford University Press, US. pp. 16. ISBN978-0-19-957485-8 .
  232. ^ Shors p. 643
  233. ^ Shors p. 631
  234. ^ Dimmock p. 272
  235. ^
  236. Baggesen DL, Sørensen G, Nielsen EM, Wegener HC (January 2010). "Phage typing of Salmonella Typhimurium – is it still a useful tool for surveillance and outbreak investigation?". Euro Surveillance. 15 (4): 19471. PMID20122382 . Retrieved 19 December 2014 .
  237. ^
  238. Parker MT (September 2016). "An Ecological Framework of the Human Virome Provides Classification of Current Knowledge and Identifies Areas of Forthcoming Discovery". The Yale Journal of Biology and Medicine. 89 (3): 339–51. PMC5045143 . PMID27698618.
  239. ^
  240. Lwoff A, Horne RW, Tournier P (June 1962). "[A virus system]". Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences (in French). 254: 4225–27. PMID14467544.
  241. ^
  242. Lwoff A, Horne R, Tournier P (1962). "A system of viruses". Cold Spring Harbor Symposia on Quantitative Biology. 27: 51–55. doi:10.1101/sqb.1962.027.001.008. PMID13931895.
  243. ^
  244. Fauquet CM, Fargette D (August 2005). "International Committee on Taxonomy of Viruses and the 3,142 unassigned species". Virology Journal. 2: 64. doi:10.1186/1743-422X-2-64. PMC1208960 . PMID16105179.
  245. ^
  246. International Committee on Taxonomy of Viruses Executive Committee (May 2020). "The New Scope of Virus Taxonomy: Partitioning the Virosphere Into 15 Hierarchical Ranks". Nat Microbiol. 5 (5): 668–674. doi:10.1038/s41564-020-0709-x. PMC7186216 . PMID32341570.
  247. ^
  248. Delwart EL (2007). "Viral metagenomics". Reviews in Medical Virology. 17 (2): 115–31. doi:10.1002/rmv.532. PMC7169062 . PMID17295196.
  249. ^
  250. Baltimore D (1974). "The strategy of RNA viruses". Harvey Lectures. 70 Series. 70 Series: 57–74. PMID4377923.
  251. ^
  252. van Regenmortel MH, Mahy BW (January 2004). "Emerging issues in virus taxonomy". Emerging Infectious Diseases. 10 (1): 8–13. doi:10.3201/eid1001.030279. PMC3322749 . PMID15078590.
  253. ^
  254. Mayo MA (1999). "Developments in plant virus taxonomy since the publication of the 6th ICTV Report. International Committee on Taxonomy of Viruses". Archives of Virology. 144 (8): 1659–66. doi:10.1007/s007050050620. PMID10486120. S2CID33422303.
  255. ^
  256. de Villiers EM, Fauquet C, Broker TR, Bernard HU, zur Hausen H (June 2004). "Classification of papillomaviruses". Virology. 324 (1): 17–27. doi:10.1016/j.virol.2004.03.033. PMID15183049.
  257. ^ Mainly Chapter 33 (Disease summaries), pp. 367–92 in:
  258. Fisher B, Harvey RP, Champe PC (2007). Lippincott's Illustrated Reviews: Microbiology. Lippincott's Illustrated Reviews Series. Hagerstwon, MD: Lippincott Williams & Wilkins. pp. 367–92. ISBN978-0-7817-8215-9 .
  259. ^
  260. Komaroff AL (December 2006). "Is human herpesvirus-6 a trigger for chronic fatigue syndrome?". Journal of Clinical Virology. 37 (Suppl 1): S39–46. doi:10.1016/S1386-6532(06)70010-5. PMID17276367.
  261. ^
  262. Chen CH, Chiu YL, Wei FC, Koong FJ, Liu HC, Shaw CK, et al. (January 1999). "High seroprevalence of Borna virus infection in schizophrenic patients, family members and mental health workers in Taiwan". Molecular Psychiatry. 4 (1): 33–38. doi: 10.1038/ . PMID10089006. S2CID19830976.
  263. ^
  264. Margolis TP, Elfman FL, Leib D, Pakpour N, Apakupakul K, Imai Y, Voytek C (October 2007). "Spontaneous reactivation of herpes simplex virus type 1 in latently infected murine sensory ganglia". Journal of Virology. 81 (20): 11069–74. doi:10.1128/JVI.00243-07. PMC2045564 . PMID17686862.
  265. ^
  266. Whitley RJ, Roizman B (May 2001). "Herpes simplex virus infections". Lancet. 357 (9267): 1513–18. doi:10.1016/S0140-6736(00)04638-9. PMID11377626. S2CID9854903.
  267. ^
  268. Barton ES, White DW, Cathelyn JS, Brett-McClellan KA, Engle M, Diamond MS, et al. (May 2007). "Herpesvirus latency confers symbiotic protection from bacterial infection". Nature. 447 (7142): 326–29. Bibcode:2007Natur.447..326B. doi:10.1038/nature05762. PMID17507983. S2CID4425405.
  269. ^
  270. Bertoletti A, Gehring A (October 2007). "Immune response and tolerance during chronic hepatitis B virus infection". Hepatology Research. 37 (Suppl 3): S331–38. doi:10.1111/j.1872-034X.2007.00221.x. PMID17931183. S2CID13386004.
  271. ^
  272. Rodrigues C, Deshmukh M, Jacob T, Nukala R, Menon S, Mehta A (2001). "Significance of HBV DNA by PCR over serological markers of HBV in acute and chronic patients". Indian Journal of Medical Microbiology. 19 (3): 141–44. PMID17664817.
  273. ^
  274. Nguyen VT, McLaws ML, Dore GJ (December 2007). "Highly endemic hepatitis B infection in rural Vietnam". Journal of Gastroenterology and Hepatology. 22 (12): 2093–100. doi:10.1111/j.1440-1746.2007.05010.x. PMID17645465. S2CID29885790.
  275. ^
  276. Fowler MG, Lampe MA, Jamieson DJ, Kourtis AP, Rogers MF (September 2007). "Reducing the risk of mother-to-child human immunodeficiency virus transmission: past successes, current progress and challenges, and future directions". American Journal of Obstetrics and Gynecology. 197 (3 Suppl): S3–9. doi:10.1016/j.ajog.2007.06.048. PMID17825648.
  277. ^
  278. Sauerbrei A, Wutzler P (December 2000). "The congenital varicella syndrome". Journal of Perinatology. 20 (8 Pt 1): 548–54. doi:10.1038/ PMID11190597. S2CID7973561.
  279. ^ ab
  280. Antonovics J, Wilson AJ, Forbes MR, Hauffe HC, Kallio ER, Leggett HC, Longdon B, Okamura B, Sait SM, Webster JP (May 2017). "The evolution of transmission mode". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 372 (1719). doi:10.1098/rstb.2016.0083. PMC5352810 . PMID28289251.
  281. ^
  282. Garnett GP (February 2005). "Role of herd immunity in determining the effect of vaccines against sexually transmitted disease". The Journal of Infectious Diseases. 191 (Suppl 1): S97–106. doi: 10.1086/425271 . PMID15627236.
  283. ^
  284. Platonov AE (2006). "[The influence of weather conditions on the epidemiology of vector-borne diseases by the example of West Nile fever in Russia]". Vestnik Rossiiskoi Akademii Meditsinskikh Nauk (in Russian) (2): 25–29. PMID16544901.
  285. ^ Shors p. 264
  286. ^ Shors pp. 894
  287. ^
  288. Jewell CP, Keeling MJ, Roberts GO (December 2009). "Predicting undetected infections during the 2007 foot-and-mouth disease outbreak". Journal of the Royal Society, Interface. 6 (41): 1145–51. doi:10.1098/rsif.2008.0433. PMC2817150 . PMID19091686.
  289. ^ Shors p. 170
  290. ^ ab Shors pp. 170–72
  291. ^ Shors p. 272
  292. ^ Shors pp. 891
  293. ^ Collier pp. 409–15
  294. ^
  295. Patterson KD, Pyle GF (1991). "The geography and mortality of the 1918 influenza pandemic". Bulletin of the History of Medicine. 65 (1): 4–21. PMID2021692.
  296. ^
  297. Johnson NP, Mueller J (2002). "Updating the accounts: global mortality of the 1918-1920 "Spanish" influenza pandemic". Bulletin of the History of Medicine. 76 (1): 105–15. doi:10.1353/bhm.2002.0022. PMID11875246. S2CID22974230.
  298. ^
  299. Eisinger RW, Fauci AS (March 2018). "1". Emerging Infectious Diseases. 24 (3): 413–16. doi:10.3201/eid2403.171797. PMC5823353 . PMID29460740.
  300. ^
  301. Qin Y, Zhao MJ, Tan YY, Li XQ, Zheng JD, Peng ZB, Feng LZ (August 2018). "[History of influenza pandemics in China during the past century]". Zhonghua Liu Xing Bing Xue Za Zhi = Zhonghua Liuxingbingxue Zazhi (in Chinese). 39 (8): 1028–31. doi:10.3760/cma.j.issn.0254-6450.2018.08.003. PMID30180422.
  302. ^
  303. Gao F, Bailes E, Robertson DL, Chen Y, Rodenburg CM, Michael SF, et al. (February 1999). "Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes". Nature. 397 (6718): 436–41. Bibcode:1999Natur.397..436G. doi:10.1038/17130. PMID9989410. S2CID4432185.
  304. ^
  305. "Fact Sheet" (PDF) . 2018 . Retrieved 12 December 2019 .
  306. ^
  307. "UN AIDS DATA2019". 2019 . Retrieved 5 December 2019 .
  308. ^
  309. Mawar N, Saha S, Pandit A, Mahajan U (December 2005). "The third phase of HIV pandemic: social consequences of HIV/AIDS stigma & discrimination & future needs" (PDF) . The Indian Journal of Medical Research. 122 (6): 471–84. PMID16517997. Archived from the original (PDF) on 4 March 2016 . Retrieved 19 December 2014 .
  310. ^
  311. "Status of the global HIV epidemic" (PDF) . UNAIDS. 2008. Archived from the original (PDF) on 22 November 2015 . Retrieved 19 December 2014 .
  312. ^
  313. Towner JS, Khristova ML, Sealy TK, Vincent MJ, Erickson BR, Bawiec DA, et al. (July 2006). "Marburgvirus genomics and association with a large hemorrhagic fever outbreak in Angola". Journal of Virology. 80 (13): 6497–516. doi:10.1128/JVI.00069-06. PMC1488971 . PMID16775337.
  314. ^
  315. "World Health Organisation report, 24 September 2014" (PDF) .
  316. ^
  317. "Virology Journal". Virology Journal.
  318. ^
  319. Weiss SR, Leibowitz JL (2011). Coronavirus pathogenesis. Advances in Virus Research. 81. pp. 85–164. doi:10.1016/B978-0-12-385885-6.00009-2. ISBN978-0-12-385885-6 . PMC7149603 . PMID22094080.
  320. ^
  321. Wong AT, Chen H, Liu SH, Hsu EK, Luk KS, Lai CK, et al. (May 2017). "From SARS to Avian Influenza Preparedness in Hong Kong". Clinical Infectious Diseases. 64 (suppl_2): S98–S104. doi: 10.1093/cid/cix123 . PMID28475794.
  322. ^
  323. Ashour HM, Elkhatib WF, Rahman MM, Elshabrawy HA (March 2020). "Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks". Pathogens. 9 (3): 186. doi:10.3390/pathogens9030186. PMC7157630 . PMID32143502.
  324. ^
  325. Deng SQ, Peng HJ (February 2020). "Characteristics of and Public Health Responses to the Coronavirus Disease 2019 Outbreak in China". Journal of Clinical Medicine. 9 (2): 575. doi:10.3390/jcm9020575. PMC7074453 . PMID32093211.
  326. ^
  327. Han Q, Lin Q, Jin S, You L (April 2020). "Coronavirus 2019-nCoV: A brief perspective from the front line". The Journal of Infection. 80 (4): 373–77. doi:10.1016/j.jinf.2020.02.010. PMC7102581 . PMID32109444.
  328. ^
  329. Londoño E, Ortiz A (16 March 2020). "Coronavirus Travel Restrictions, Across the Globe" – via
  330. ^
  331. "US takes more big pandemic response steps Europe COVID-19 cases soar". CIDRAP.
  332. ^
  333. Einstein MH, Schiller JT, Viscidi RP, Strickler HD, Coursaget P, Tan T, et al. (June 2009). "Clinician's guide to human papillomavirus immunology: knowns and unknowns". The Lancet. Infectious Diseases. 9 (6): 347–56. doi:10.1016/S1473-3099(09)70108-2. PMID19467474.
  334. ^
  335. Shuda M, Feng H, Kwun HJ, Rosen ST, Gjoerup O, Moore PS, Chang Y (October 2008). "T antigen mutations are a human tumor-specific signature for Merkel cell polyomavirus". Proceedings of the National Academy of Sciences of the United States of America. 105 (42): 16272–77. Bibcode:2008PNAS..10516272S. doi:10.1073/pnas.0806526105. PMC2551627 . PMID18812503.
  336. ^
  337. Pulitzer MP, Amin BD, Busam KJ (May 2009). "Merkel cell carcinoma: review". Advances in Anatomic Pathology. 16 (3): 135–44. doi:10.1097/PAP.0b013e3181a12f5a. PMID19395876. S2CID36110778.
  338. ^
  339. Koike K (June 2007). "Hepatitis C virus contributes to hepatocarcinogenesis by modulating metabolic and intracellular signaling pathways". Journal of Gastroenterology and Hepatology. 22 (Suppl 1): S108–11. doi:10.1111/j.1440-1746.2006.04669.x. PMID17567457. S2CID25399220.
  340. ^
  341. Hu J, Ludgate L (2007). "HIV-HBV and HIV-HCV coinfection and liver cancer development". Cancer Treatment and Research. 133: 241–52. doi:10.1007/978-0-387-46816-7_9. ISBN978-0-387-46804-4 . PMID17672044.
  342. ^
  343. Bellon M, Nicot C (2007). "Telomerase: a crucial player in HTLV-I-induced human T-cell leukemia". Cancer Genomics & Proteomics. 4 (1): 21–25. PMID17726237.
  344. ^
  345. Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S (September 2007). "Human papillomavirus and cervical cancer". Lancet. 370 (9590): 890–907. doi:10.1016/S0140-6736(07)61416-0. PMID17826171. S2CID20196938.
  346. ^
  347. Klein E, Kis LL, Klein G (February 2007). "Epstein-Barr virus infection in humans: from harmless to life endangering virus-lymphocyte interactions". Oncogene. 26 (9): 1297–305. doi: 10.1038/sj.onc.1210240 . PMID17322915.
  348. ^
  349. Zur Hausen H (July 2008). "Novel human polyomaviruses – re-emergence of a well known virus family as possible human carcinogens". International Journal of Cancer. 123 (2): 247–50. doi: 10.1002/ijc.23620 . PMID18449881. S2CID9482506.
  350. ^
  351. Alberta B, Johnson A, Lewis J, Raff M, Roberts K, Walters P (2002). Molecular Biology of the Cell (Fourth ed.). New York and London: Garland Science. ISBN0-8153-3218-1 .
  352. ^
  353. Ding SW, Voinnet O (August 2007). "Antiviral immunity directed by small RNAs". Cell. 130 (3): 413–26. doi:10.1016/j.cell.2007.07.039. PMC2703654 . PMID17693253.
  354. ^
  355. Patton JT, Vasquez-Del Carpio R, Spencer E (2004). "Replication and transcription of the rotavirus genome". Current Pharmaceutical Design. 10 (30): 3769–77. doi:10.2174/1381612043382620. PMID15579070.
  356. ^
  357. Jayaram H, Estes MK, Prasad BV (April 2004). "Emerging themes in rotavirus cell entry, genome organization, transcription and replication". Virus Research. 101 (1): 67–81. doi:10.1016/j.virusres.2003.12.007. PMID15010218.
  358. ^
  359. Greer S, Alexander GJ (December 1995). "Viral serology and detection". Bailliere's Clinical Gastroenterology. 9 (4): 689–721. doi:10.1016/0950-3528(95)90057-8. PMID8903801.
  360. ^
  361. Matter L, Kogelschatz K, Germann D (April 1997). "Serum levels of rubella virus antibodies indicating immunity: response to vaccination of subjects with low or undetectable antibody concentrations". The Journal of Infectious Diseases. 175 (4): 749–55. doi: 10.1086/513967 . PMID9086126.
  362. ^
  363. Mallery DL, McEwan WA, Bidgood SR, Towers GJ, Johnson CM, James LC (November 2010). "Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21)". Proceedings of the National Academy of Sciences of the United States of America. 107 (46): 19985–90. Bibcode:2010PNAS..10719985M. doi:10.1073/pnas.1014074107. PMC2993423 . PMID21045130.
  364. ^
  365. Cascalho M, Platt JL (2007). "Novel functions of B cells". Critical Reviews in Immunology. 27 (2): 141–51. doi:10.1615/critrevimmunol.v27.i2.20. PMID17725500.
  366. ^
  367. Le Page C, Génin P, Baines MG, Hiscott J (2000). "Interferon activation and innate immunity". Reviews in Immunogenetics. 2 (3): 374–86. PMID11256746.
  368. ^
  369. Hilleman MR (October 2004). "Strategies and mechanisms for host and pathogen survival in acute and persistent viral infections". Proceedings of the National Academy of Sciences of the United States of America. 101 (Suppl 2): 14560–66. Bibcode:2004PNAS..10114560H. doi:10.1073/pnas.0404758101. PMC521982 . PMID15297608.
  370. ^
  371. Asaria P, MacMahon E (October 2006). "Measles in the United Kingdom: can we eradicate it by 2010?". BMJ. 333 (7574): 890–95. doi:10.1136/bmj.38989.445845.7C. PMC1626346 . PMID17068034.
  372. ^
  373. Lane JM (2006). "Mass vaccination and surveillance/containment in the eradication of smallpox". Current Topics in Microbiology and Immunology. 304: 17–29. doi:10.1007/3-540-36583-4_2. ISBN978-3-540-29382-8 . PMC7120753 . PMID16989262.
  374. ^
  375. Arvin AM, Greenberg HB (January 2006). "New viral vaccines". Virology. 344 (1): 240–49. doi: 10.1016/j.virol.2005.09.057 . PMID16364754.
  376. ^
  377. Pastoret PP, Schudel AA, Lombard M (August 2007). "Conclusions--future trends in veterinary vaccinology". Revue Scientifique et Technique. 26 (2): 489–94, 495–501, 503–09. doi:10.20506/rst.26.2.1759. PMID17892169.
  378. ^
  379. Palese P (January 2006). "Making better influenza virus vaccines?". Emerging Infectious Diseases. 12 (1): 61–65. doi:10.3201/eid1201.051043. PMC3291403 . PMID16494719.
  380. ^
  381. Thomssen R (1975). "Live attenuated versus killed virus vaccines". Monographs in Allergy. 9: 155–76. PMID1090805.
  382. ^
  383. McLean AA (1986). "Development of vaccines against hepatitis A and hepatitis B". Reviews of Infectious Diseases. 8 (4): 591–98. doi:10.1093/clinids/8.4.591. PMID3018891.
  384. ^
  385. Casswall TH, Fischler B (October 2005). "Vaccination of the immunocompromised child". Expert Review of Vaccines. 4 (5): 725–38. doi:10.1586/14760584.4.5.725. PMID16221073. S2CID40821818.
  386. ^
  387. Barnett ED, Wilder-Smith A, Wilson ME (July 2008). "Yellow fever vaccines and international travelers". Expert Review of Vaccines. 7 (5): 579–87. doi:10.1586/14760584.7.5.579. PMID18564013. S2CID19352868.
  388. ^
  389. Magden J, Kääriäinen L, Ahola T (March 2005). "Inhibitors of virus replication: recent developments and prospects". Applied Microbiology and Biotechnology. 66 (6): 612–21. doi:10.1007/s00253-004-1783-3. PMC7082807 . PMID15592828.
  390. ^
  391. Mindel A, Sutherland S (September 1983). "Genital herpes - the disease and its treatment including intravenous acyclovir". The Journal of Antimicrobial Chemotherapy. 12 (Suppl B): 51–59. doi:10.1093/jac/12.suppl_b.51. PMID6355051.
  392. ^
  393. Palmisano L, Vella S (2011). "A brief history of antiretroviral therapy of HIV infection: success and challenges". Annali dell'Istituto Superiore di Sanità. 47 (1): 44–48. doi:10.4415/ANN_11_01_10. PMID21430338.
  394. ^
  395. Witthöft T, Möller B, Wiedmann KH, Mauss S, Link R, Lohmeyer J, et al. (November 2007). "Safety, tolerability and efficacy of peginterferon alpha-2a and ribavirin in chronic hepatitis C in clinical practice: The German Open Safety Trial". Journal of Viral Hepatitis. 14 (11): 788–96. doi:10.1111/j.1365-2893.2007.00871.x. PMC2156112 . PMID17927615.
  396. ^
  397. Rudin D, Shah SM, Kiss A, Wetz RV, Sottile VM (November 2007). "Interferon and lamivudine vs. interferon for hepatitis B e antigen-positive hepatitis B treatment: meta-analysis of randomized controlled trials". Liver International. 27 (9): 1185–93. doi:10.1111/j.1478-3231.2007.01580.x. PMC2156150 . PMID17919229.
  398. ^ Dimmock p. 3
  399. ^
  400. Goris N, Vandenbussche F, De Clercq K (April 2008). "Potential of antiviral therapy and prophylaxis for controlling RNA viral infections of livestock". Antiviral Research. 78 (1): 170–78. doi:10.1016/j.antiviral.2007.10.003. PMID18035428.
  401. ^
  402. Carmichael LE (2005). "An annotated historical account of canine parvovirus". Journal of Veterinary Medicine. B, Infectious Diseases and Veterinary Public Health. 52 (7–8): 303–11. doi:10.1111/j.1439-0450.2005.00868.x. PMID16316389.
  403. ^
  404. Chen Y, Zhao Y, Hammond J, Hsu HT, Evans J, Feldlaufer M (October–November 2004). "Multiple virus infections in the honey bee and genome divergence of honey bee viruses". Journal of Invertebrate Pathology. 87 (2–3): 84–93. doi:10.1016/j.jip.2004.07.005. PMID15579317.
  405. ^ Shors p. 802
  406. ^ Shors pp. 799–807
  407. ^
  408. Zaheer K, Akhtar MH (2016). "Potato Production, Usage, and Nutrition – A Review". Critical Reviews in Food Science and Nutrition. 56 (5): 711–21. doi:10.1080/10408398.2012.724479. PMID24925679. S2CID33074838.
  409. ^
  410. Fuentes S, Jones RA, Matsuoka H, Ohshima K, Kreuze J, Gibbs AJ (July 2019). "Potato virus Y the Andean connection". Virus Evolution. 5 (2): vez037. doi:10.1093/ve/vez037. PMC6755682 . PMID31559020.
  411. ^
  412. Dinesh-Kumar SP, Tham WH, Baker BJ (December 2000). "Structure-function analysis of the tobacco mosaic virus resistance gene N". Proceedings of the National Academy of Sciences of the United States of America. 97 (26): 14789–94. Bibcode:2000PNAS. 9714789D. doi:10.1073/pnas.97.26.14789. PMC18997 . PMID11121079.
  413. ^ Shors pp. 809
  414. ^
  415. Soosaar JL, Burch-Smith TM, Dinesh-Kumar SP (October 2005). "Mechanisms of plant resistance to viruses". Nature Reviews. Microbiology. 3 (10): 789–98. doi:10.1038/nrmicro1239. PMID16132037. S2CID27311732.
  416. ^
  417. Lomonossoff GP (2011). "Virus Particles and the Uses of Such Particles in Bio- and Nanotechnology". Recent Advances in Plant Virology. Caister Academic Press. ISBN978-1-904455-75-2 .
  418. ^
  419. Wommack KE, Colwell RR (March 2000). "Virioplankton: viruses in aquatic ecosystems". Microbiology and Molecular Biology Reviews. 64 (1): 69–114. doi:10.1128/MMBR.64.1.69-114.2000. PMC98987 . PMID10704475.
  420. ^
  421. Bergh O, Børsheim KY, Bratbak G, Heldal M (August 1989). "High abundance of viruses found in aquatic environments". Nature. 340 (6233): 467–68. Bibcode:1989Natur.340..467B. doi:10.1038/340467a0. PMID2755508. S2CID4271861.
  422. ^ Shors pp. 834–35
  423. ^
  424. Bickle TA, Krüger DH (June 1993). "Biology of DNA restriction". Microbiological Reviews. 57 (2): 434–50. doi:10.1128/MMBR.57.2.434-450.1993. PMC372918 . PMID8336674.
  425. ^
  426. Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S, et al. (March 2007). "CRISPR provides acquired resistance against viruses in prokaryotes". Science. 315 (5819): 1709–12. Bibcode:2007Sci. 315.1709B. doi:10.1126/science.1138140. hdl: 20.500.11794/38902 . PMID17379808. S2CID3888761.
  427. ^
  428. Brouns SJ, Jore MM, Lundgren M, Westra ER, Slijkhuis RJ, Snijders AP, et al. (August 2008). "Small CRISPR RNAs guide antiviral defense in prokaryotes". Science. 321 (5891): 960–64. Bibcode:2008Sci. 321..960B. doi:10.1126/science.1159689. PMC5898235 . PMID18703739.
  429. ^
  430. Mojica FJ, Rodriguez-Valera F (September 2016). "The discovery of CRISPR in archaea and bacteria". The FEBS Journal. 283 (17): 3162–69. doi:10.1111/febs.13766. hdl: 10045/57676 . PMID27234458. S2CID42827598.
  431. ^
  432. Prangishvili D, Garrett RA (April 2004). "Exceptionally diverse morphotypes and genomes of crenarchaeal hyperthermophilic viruses" (PDF) . Biochemical Society Transactions. 32 (Pt 2): 204–08. doi:10.1042/BST0320204. PMID15046572.
  433. ^
  434. Mojica FJ, Díez-Villaseñor C, García-Martínez J, Soria E (February 2005). "Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements". Journal of Molecular Evolution. 60 (2): 174–82. Bibcode:2005JMolE..60..174M. doi:10.1007/s00239-004-0046-3. PMID15791728. S2CID27481111.
  435. ^
  436. Makarova KS, Grishin NV, Shabalina SA, Wolf YI, Koonin EV (March 2006). "A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action". Biology Direct. 1: 7. doi:10.1186/1745-6150-1-7. PMC1462988 . PMID16545108.
  437. ^
  438. van der Oost J, Westra ER, Jackson RN, Wiedenheft B (July 2014). "Unravelling the structural and mechanistic basis of CRISPR-Cas systems". Nature Reviews. Microbiology. 12 (7): 479–92. doi:10.1038/nrmicro3279. PMC4225775 . PMID24909109.
  439. ^
  440. Dávila-Ramos S, Castelán-Sánchez HG, Martínez-Ávila L, Sánchez-Carbente MD, Peralta R, Hernández-Mendoza A, et al. (2019). "A Review on Viral Metagenomics in Extreme Environments". Frontiers in Microbiology. 10: 2403. doi:10.3389/fmicb.2019.02403. PMC6842933 . PMID31749771.
  441. ^
  442. Zhang QY, Gui JF (December 2018). "Diversity, evolutionary contribution and ecological roles of aquatic viruses". Science China. Life Sciences. 61 (12): 1486–1502. doi:10.1007/s11427-018-9414-7. PMID30443861. S2CID53564176.
  443. ^
  444. Weitz JS, Wilhelm SW (2013). "An ocean of viruses". The Scientist. 27 (7): 35–39.
  445. ^
  446. Suttle CA (September 2005). "Viruses in the sea". Nature. 437 (7057): 356–61. Bibcode:2005Natur.437..356S. doi:10.1038/nature04160. PMID16163346. S2CID4370363.
  447. ^
  448. Wilhelm SW, Suttle CA (1999). "Viruses and nutrient cycles in the sea: viruses play critical roles in the structure and function of aquatic food webs". BioScience. 49 (10): 781–88. doi: 10.2307/1313569 . JSTOR1313569.
  449. ^
  450. Shelford EJ, Suttle CA (2018). "Virus-mediated transfer of nitrogen from heterotrophic bacteria to phytoplankton". Biogeosciences. 15 (3): 809–15. Bibcode:2018BGeo. 15..809S. doi: 10.5194/bg-15-809-2018 .
  451. ^ abcd
  452. Suttle CA (October 2007). "Marine viruses – major players in the global ecosystem". Nature Reviews. Microbiology. 5 (10): 801–12. doi:10.1038/nrmicro1750. PMID17853907. S2CID4658457.
  453. ^
  454. Wigington CH, Sonderegger D, Brussaard CP, Buchan A, Finke JF, Fuhrman JA, et al. (January 2016). "Re-examination of the relationship between marine virus and microbial cell abundances" (PDF) . Nature Microbiology. 1 (15024): 15024. doi:10.1038/nmicrobiol.2015.24. PMID27572161. S2CID52829633.
  455. ^
  456. Brussaard CP (2004). "Viral control of phytoplankton populations – a review". The Journal of Eukaryotic Microbiology. 51 (2): 125–38. doi:10.1111/j.1550-7408.2004.tb00537.x. PMID15134247. S2CID21017882.
  457. ^
  458. Robbins J (13 April 2018). "Trillions Upon Trillions of Viruses Fall From the Sky Each Day". The New York Times . Retrieved 14 April 2018 .
  459. ^
  460. Reche I, D'Orta G, Mladenov N, Winget DM, Suttle CA (April 2018). "Deposition rates of viruses and bacteria above the atmospheric boundary layer". The ISME Journal. 12 (4): 1154–62. doi:10.1038/s41396-017-0042-4. PMC5864199 . PMID29379178.
  461. ^
  462. Hall AJ, Jepson PD, Goodman SJ, Harkonen T (2006). "Phocine distemper virus in the North and European Seas – data and models, nature and nurture". Biological Conservation. 131 (2): 221–29. doi:10.1016/j.biocon.2006.04.008.
  463. ^
  464. Broecker F, Moelling K (2019). "What viruses tell us about evolution and immunity: beyond Darwin?". Annals of the New York Academy of Sciences. 1447 (1): 53–68. doi: 10.1111/nyas.14097 . PMC6850104 . PMID31032941.
  465. ^
  466. Forterre P, Philippe H (June 1999). "The last universal common ancestor (LUCA), simple or complex?". The Biological Bulletin. 196 (3): 373–75, discussion 375–77. doi:10.2307/1542973. JSTOR1542973. PMID11536914.
  467. ^ Collier p. 8
  468. ^
  469. Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J (2000). "Viruses: Structure, Function, and Uses". Molecular Cell Biology (4th ed.). New York: W. H. Freeman.
  470. ^
  471. Matsuzaki S, Rashel M, Uchiyama J, Sakurai S, Ujihara T, Kuroda M, et al. (October 2005). "Bacteriophage therapy: a revitalized therapy against bacterial infectious diseases". Journal of Infection and Chemotherapy. 11 (5): 211–19. doi:10.1007/s10156-005-0408-9. PMID16258815. S2CID8107934.
  472. ^
  473. Gleba YY, Giritch A (2011). "Plant Viral Vectors for Protein Expression". Recent Advances in Plant Virology. Caister Academic Press. ISBN978-1-904455-75-2 .
  474. ^
  475. Jefferson A, Cadet VE, Hielscher A (September 2015). "The mechanisms of genetically modified vaccinia viruses for the treatment of cancer". Critical Reviews in Oncology/Hematology. 95 (3): 407–16. doi:10.1016/j.critrevonc.2015.04.001. PMID25900073.
  476. ^
  477. Karimkhani C, Gonzalez R, Dellavalle RP (August 2014). "A review of novel therapies for melanoma". American Journal of Clinical Dermatology. 15 (4): 323–37. doi:10.1007/s40257-014-0083-7. PMID24928310. S2CID38864550.
  478. ^
  479. "FDA approves Amgen's injected immunotherapy for melanoma". Reuters. 27 October 2015 . Retrieved 24 January 2020 .
  480. ^
  481. Burke J, Nieva J, Borad MJ, Breitbach CJ (August 2015). "Oncolytic viruses: perspectives on clinical development". Current Opinion in Virology. 13: 55–60. doi:10.1016/j.coviro.2015.03.020. PMID25989094.
  482. ^
  483. Dogic Z (2016). "Filamentous Phages As a Model System in Soft Matter Physics". Frontiers in Microbiology. 7: 1013. doi:10.3389/fmicb.2016.01013. PMC4927585 . PMID27446051.
  484. ^
  485. Fischlechner M, Donath E (2007). "Viruses as building blocks for materials and devices". Angewandte Chemie. 46 (18): 3184–93. doi:10.1002/anie.200603445. PMID17348058.
  486. ^
  487. Soto CM, Blum AS, Vora GJ, Lebedev N, Meador CE, Won AP, et al. (April 2006). "Fluorescent signal amplification of carbocyanine dyes using engineered viral nanoparticles". Journal of the American Chemical Society. 128 (15): 5184–89. doi:10.1021/ja058574x. PMID16608355.
  488. ^
  489. Blum AS, Soto CM, Wilson CD, Brower TL, Pollack SK, Schull TL, et al. (July 2005). "An engineered virus as a scaffold for three-dimensional self-assembly on the nanoscale". Small. 1 (7): 702–06. doi:10.1002/smll.200500021. PMID17193509.
  490. ^
  491. Cello J, Paul AV, Wimmer E (August 2002). "Chemical synthesis of poliovirus cDNA: generation of infectious virus in the absence of natural template". Science. 297 (5583): 1016–18. Bibcode:2002Sci. 297.1016C. doi:10.1126/science.1072266. PMID12114528. S2CID5810309.
  492. ^
  493. Coleman JR, Papamichail D, Skiena S, Futcher B, Wimmer E, Mueller S (June 2008). "Virus attenuation by genome-scale changes in codon pair bias". Science. 320 (5884): 1784–87. Bibcode:2008Sci. 320.1784C. doi:10.1126/science.1155761. PMC2754401 . PMID18583614.
  494. ^
  495. "NIH viral genome database". . Retrieved 5 February 2021 .
  496. ^
  497. Zilinskas RA (August 2017). "A brief history of biological weapons programmes and the use of animal pathogens as biological warfare agents". Revue Scientifique et Technique (International Office of Epizootics). 36 (2): 415–422. doi:10.20506/rst.36.2.2662. PMID30152475.
  498. ^ abc
  499. Artenstein AW, Grabenstein JD (October 2008). "Smallpox vaccines for biodefense: need and feasibility". Expert Review of Vaccines. 7 (8): 1225–37. doi:10.1586/14760584.7.8.1225. PMID18844596. S2CID33855724.


  • Collier L, Balows A, Sussman M (1998). Mahy B, Collier LA (eds.). Topley and Wilson's Microbiology and Microbial Infections. Virology. 1 (Ninth ed.). ISBN0-340-66316-2 .
  • Dimmock NJ, Easton AJ, Leppard K (2007). Introduction to Modern Virology (Sixth ed.). Blackwell Publishing. ISBN978-1-4051-3645-7 .
  • Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B, Straus SE (2007). Fields Virology. Lippincott Williams & Wilkins. ISBN978-0-7817-6060-7 .
  • Shors T (2017). Understanding Viruses. Jones and Bartlett Publishers. ISBN978-1-284-02592-7 .
    Media related to Viruses at Wikimedia Commons Data related to Virus at Wikispecies A Swiss Institute of Bioinformatics resource for all viral families, providing general molecular and epidemiological information

140 ms 7.2% Scribunto_LuaSandboxCallback::gsub 140 ms 7.2% Scribunto_LuaSandboxCallback::callParserFunction 120 ms 6.2% Scribunto_LuaSandboxCallback::find 100 ms 5.2% 80 ms 4.1% Scribunto_LuaSandboxCallback::getEntity 80 ms 4.1% recursiveClone 80 ms 4.1% Scribunto_LuaSandboxCallback::match 60 ms 3.1% Scribunto_LuaSandboxCallback::getExpandedArgument 60 ms 3.1% [others] 720 ms 37.1% Number of Wikibase entities loaded: 6/400 -->

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Original Source Articles

(1) Leibman-Markus, M., Pizarro, L., Schuster, S., Daniel Lin, Z. J., Gershony, O., Bar, M., et al. 2018. The intracellular nucleotide-binding leucine-rich repeat receptor (SlNRC4a) enhances immune signaling elicited by extracellular perception. Plant Cell Environ. 51:2313�. doi: 10.1111/pce.13347

(2) Pizarro, L., Leibman-Markus, M., Gupta, R., Kovetz, N., Shtein, I., Bar, E., et al. 2020. A gain of function mutation in SlNRC4a enhances basal immunity resulting in broad-spectrum disease resistance. Commun. Biol. 3:404. doi: 10.1038/s42003-020-01130-w


[1] Alhoraibi, H., Bigeard, J., Rayapuram, N., Colcombet, J., and Hirt, H. 2019. Plant immunity: the MTI-ETI model and beyond. Curr. Issues Mol. Biol. 30:39�. doi: 10.21775/cimb.030.039

[2] Flor, H. H. 1971. Current status of gene-for-gene concept. Annu. Rev. Phytopathol. 9:275�. doi: 10.1146/

[3] Jones, J. D., and Dangl, J. L. 2006. The plant immune system. Nature 444:323𠄹. doi: 10.1038/nature05286

[4] Medzhitov, R., and Janeway, C. A. Jr. 1997. Innate immunity: the virtues of a nonclonal system of recognition. Cell 91:295𠄸.

[5] Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., and Charpentier, E. 2012. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337:816�. doi: 10.1126/science.1225829

[6] Pizarro, L., Leibman-Markus, M., Gupta, R., Kovetz, N., Shtein, I., Bar, E., et al. 2020. A gain of function mutation in SlNRC4a enhances basal immunity resulting in broad-spectrum disease resistance. Commun. Biol. 3:404. doi: 10.1038/s42003-020-01130-w

Watch the video: Τι τρέχει τελικά με τα mRNA. DNA εμβόλια? (January 2022).