Information

15.3.1.2B: Influenza - Biology


Influenza is a viral infection of the lungs characterized by fever, cough, and severe muscle aches. Influenza is not a case of low fever and sniffles that keeps you home in bed for a day nor a gastrointestinal upset ("stomach flu").

Influenza was responsible for the most devastating plague in human history - the "Spanish" flu that swept around the world in 1918 killing 675,000 people in the U.S. and an estimated 20–50 million people worldwide. (A disease that attacks a large fraction of the population in every region of the world is called a pandemic.) (It is uncertain where the flu first appeared, but it certainly wasn't in Spain.)

No one at the time even knew what disease agent was causing the pandemic. Not until 1930 (in pigs) and 1933 (in humans) was it established that influenza is caused by a virus.

This electron micrograph (courtesy of Dr. K. G. Murti) shows several influenza virus particles (at a magnification of about 265,000x). The surface projections are molecules of hemagglutinin and neuraminidase (see below).

There are three types of influenza:

  • Common but seldom causes disease symptoms.
  • Often causes sporadic outbreaks of illness, especially in residential communities like nursing homes.
  • Responsible for regular outbreaks, including the one of 1918. Influenza A viruses also infect domestic animals (pigs, horses, chickens, ducks) and some wild birds.

The Influenza A Virus

The influenza A virion is

  • a globular particle (about 100 nm in diameter)
  • sheathed in a lipid bilayer (derived from the plasma membrane of its host)
  • Studded in the lipid bilayer are three integral membrane proteins
    • some 500 molecules of hemagglutinin ("H")
    • some 100 molecules of neuraminidase ("N")
    • the M2 membrane protein (not shown).
  • Encased by the lipid bilayer are
    • some 3000 molecules of matrix protein
    • 8 pieces or segments of RNA

Each of the 8 RNA molecules is associated with

  • many copies of a nucleoprotein
  • the three subunits of its RNA polymerase
  • some "non-structural" protein molecules of uncertain function

The Disease

The influenza virus invades cells of the respiratory passages.

  • Its hemagglutinin molecules bind to sialic acid residues on the glycoproteins exposed at the surface of the epithelial cells of the host respiratory system.
  • The virus is engulfed by receptor mediated endocytosis.
  • The drop in pH in the endosome (endocytic vesicle) produces a change in the structure of the viral hemagglutinin enabling it to
  • fuse the viral membrane with the vesicle membrane.
  • This exposes the contents of the virus to the cytosol.
  • The RNA enter the nucleus of the cell where fresh copies are made.
  • These return to the cytosol where some serve as messenger RNA (mRNA) molecules to be translated into the proteins of fresh virus particles.
  • Fresh virus buds off from the plasma membrane of the cell (aided by the M2 protein) thus
  • spreading the infection to new cells.

The result is a viral pneumonia. It usually does not kill the patient (the 1918 pandemic was an exception; some victims died within hours) but does expose the lungs to infection by various bacterial invaders that can be lethal. Before the discovery of the flu virus, the bacterium Hemophilus influenzae was so often associated with the disease that it gave it its name.

Pandemics and Antigenic Shift

Three pandemics of influenza have swept the world since the "Spanish" flu of 1918.

  • The "Asian" flu pandemic of 1957;
  • the "Hong Kong" flu pandemic of 1968;
  • the "Swine" flu pandemic that began in April of 2009.

The pandemic of 1957 probably made more people sick than the one of 1918. But the availability of antibiotics to treat the secondary infections that are the usual cause of death resulted in a much lower death rate. The hemagglutinin of the 1918 flu virus was H1, its neuraminidase was N1, so it is designated as an H1N1 "subtype". Here are some others.

Some example strains of influenza A
DateStrainSubtypeNotes
1918H1N1pandemic of "Spanish" flu
1957A/Singapore/57H2N2pandemic of "Asian" flu
1962A/Japan/62H2N2epidemic
1964A/Taiwan/64H2N2epidemic
1968A/Aichi/68H3N2pandemic of "Hong Kong" flu
1976A/New Jersey/76H1N1swine flu in recruits
1977A/USSR/77H1N1"Russian" flu
2009A/California/09H1N1pandemic of "swine" flu [now designated A(H1N1)pdm09]

Until 2009, these data suggest that flu pandemics occur when the virus acquires a new hemagglutinin and/or neuraminidase. For this reason, when an H1N1 virus appeared in a few recruits at Fort Dix in New Jersey in 1976, it triggered a massive immunization program (which turned out not to be needed). However, an H1N1 virus appeared the following year (perhaps escaped from a laboratory) causing the "Russian" flu. We now know that this virus was a direct descendant of the 1918 flu. While accumulating mutations that made it less dangerous, it had been infecting humans until it was replaced by the H2N2 "Asian" flu of 1957. Because most people born before the Asian flu pandemic of 1957 had been exposed to the H1N1 viruses circulating before, the Russian flu primarily affected children and young adults. For the same reason, this pattern was also seen in the 2009-10 pandemic of "swine" flu.

Where do the new H or N molecules come from?

Birds appear to be the source. Both the H2 that appeared in 1957 and the H3 that appeared in 1968 came from influenza viruses circulating in birds. The encoding of H and N by separate RNA molecules probably facilitates the reassortment of these genes in animals simultaneously infected by two different subtypes. For example, H3N1 virus has been recovered from pigs simultaneously infected with swine flu virus (H1N1) and the Hong King virus (H3N2). Probably reassortment can also occur in humans with dual infections.

Epidemics and Antigenic Drift

No antigenic shifts occurred between 1957 ("Asian") and 1968 ("Hong Kong"). So what accounts for the epidemics of 1962 and 1964? Missense mutations in the hemagglutinin (H) gene. Flu infections create a strong antibody response. After a pandemic or major epidemic, most people will be immune to the virus strain that caused it. The flu virus has two options:

  • wait until a new crop of susceptible young people comes along
  • change the epitopes on the hemagglutinin molecule (and, to a lesser degree, the neuraminidase) so that they are no longer recognized by the antibodies circulating in the bodies of previous victims.
    • By 1972, the H3 molecules of the circulating strains differed in 18 amino acids from the original "Hong Kong" strain
    • By 1975, the difference had increased to 29 amino acids.

The gradual accumulation of new epitopes on the H (and N) molecules of flu viruses is called antigenic drift. Spontaneous mutations in the H (or N) gene give their owners a selective advantage as the host population becomes increasingly immune to the earlier strains.

Flu Vaccines

Although a case of the flu elicits a strong immune response against the strain that caused it, the speed with which new strains arise by antigenic drift soon leaves one susceptible to a new infection. Immunization with flu vaccines has proved moderately helpful in reducing the size and severity of new epidemics.

Some vaccines incorporate inactivated virus particles; others use the purified hemagglutinin and neuraminidase. Both types incorporate antigens from the three major strains in circulation, currently:

  • an A strain of the H1N1 subtype
  • an A strain of the H3N2 subtype and
  • a B strain.

Because of antigenic drift, the strains used must be changed periodically as new strains emerge that are no longer controlled by people's residual immunity.

The process:

  • Chicken eggs are infected with the virus expressing the new H and/or N and simultaneously infected with a stock flu virus that grows very well in eggs.
  • Genetic reassortment produces some viruses with both the new H and N genes along with the 8 other genes from the stock strain.
  • This new virus is then grown in massive amounts and the H and N proteins purified for the new vaccine.

The whole process takes several weeks. A promising way to speed things up is to chemically synthesize the new H and N genes and substitute them for the H and N genes in the stock virus. The new virus can be ready for vaccine production in a few days.

Examples of Flu Vaccines (for those who are interested)

In 17 June 2003, the U. S. Food and Drug Administration (FDA) approved FluMist® – a live-virus vaccine that is given as a spray up the nose. The viruses have been weakened so that they do not cause illness, but are able to replicate in the relatively cool tissues of the nasopharynx where they can induce an immune response. Presumably this is tilted towards IgA production, a better defense against infection by inhaled viruses than blood-borne IgG antibodies. In any case, FluMist® induces a more rapid response than inactivated vaccine and there is some evidence that it provides better protection against antigenic drift as well.

All three currently-circulating strains of flu (H1N1, H3N2, and B) are included. As new strains appear, they can be substituted.

At present, this new vaccine (technically known as LAIV "Live Attenuated Influenza Vaccine") is only approved for children older than 24 months and adults younger than 50. People with immunodeficiency (e.g., AIDS) should also be cautious about taking it.

Update: For as yet unknown reasons, the nasal spray did not work during the 2015–2016 season, and it is not recommended for the upcoming season.

Flublok®

On 16 January 2013, the U. FDA approved an entirely new type of vaccine. Flublok® is made in cell cultures transformed with recombinant DNA encoding the hemagglutinins of the 3 currently circulating flu strains (H1N1, H3N2, and B). The final concentration of antigens is three times that in the current vaccine. Cultures of insect cells are used so there is no problem with possible egg allergies in those receiving the vaccine.

Other weapons against flu

It takes a while for the flu vaccine to build up a protective level of antibodies. What if you neglected to get your flu shot and now an epidemic has arrived?

Amantadine and Rimantadine

These drugs inhibit the M2 matrix protein needed to get viral RNA into the cytosol. They work against A strains only, and resistance to the drugs evolves quickly. By the 2009-2010 flu season, virtually all strains of both H3N2 and H1N1 had developed resistance.

Zanamivir (Relenza®) and Oseltamivir (Tamiflu®)

These drugs block the neuraminidase and thus inhibit the release and spread of fresh virions. Spraying zanamivir into the nose or inhaling it shortens the duration of disease symptoms by one to three days. Unfortunately, by the 2008-2009 flu season, all H1N1 strains circulating in the U.S. had become resistant to Tamiflu.

Antibiotics

Antibiotics are of absolutely no value against the flu virus. However, they are often given to patients to combat the secondary bacterial infections that occur and that are usually the main cause of serious illness and death.

Why so few drugs?

The mechanisms by which amantadine and zanamivir work provide a clue. There are far fewer anti-viral drugs than antibacterial drugs because so much of the virus life cycle is dependent on the machinery of its host. There are many agents that could kill off the virus, but they would kill off host cell as well. So the goal is to find drugs that target molecular machinery unique to the virus. The more we learn about these molecular details, the better the chance for developing a successful new drug.

The "Spanish" Flu

Jeffery Taubenberger and his colleagues have sequenced the genes of the influenza virus that had been recovered from

  • preserved lung tissue of a U.S. soldier who died from influenza in 1918
  • lung tissue from a flu victim whose body had remained frozen in the permafrost of Alaska since she died in 1918

But even with all of its genes now completely sequenced, why the 1918 strain was so deadly is not fully understood. But deadly it is. They have even been able to replace the 8 genes of a laboratory strain of flu virus with all 8 genes of the 1918 strain (using strict biosafety containment procedures!). The resulting virus kills mice faster than any other human flu virus tested. (Reported in the 7 October 2005 issue of Science.)

The Swine Flu of 2009

A new H1N1 flu began infecting humans in North America in April 2009 and has now spread throughout much of the world. Sequencing its genome revealed a novel virus - now called A(H1N1)pdm09 - that contained genes previously found in four different strains of swine flu:

  • an HA gene (H1) derived from the swine flu of 1930 (and closely-related to the H1 of the great 1918 "Spanish" flu pandemic) along with an NP and NS gene from that virus;
  • an NA gene (N1) from a virus that had been circulating in the pigs of Europe and Asia since 1979 along with the M gene from that virus;
  • a PA and PB2 gene that entered pigs from birds around 1998;
  • a PB1 gene that passed from birds to humans around 1968 and from us to pigs around 1998.

Why this remarkable assortment of genes has enabled he virus to jump so successfully from pigs to humans remains to be determined.

The amino acid sequence around the critical epitopes of its H1 molecules closely resemble those found in the resurrected 1918 flu virus. This would explain why

  • Antibodies from elderly survivors of the 1918 pandemic neutralize the new swine flu virus.
  • Antibodies (raised in mice) to the new swine flu virus neutralize the resurrected 1918 flu virus.
  • The recent pandemic caused serious illness and death mostly in young adults and least in children and the elderly. As for the elderly, this contrast to the usual pattern arose because people over 65, even if not old enough to have been exposed to the 1918 virus, had been exposed to H1 viruses that until 1957 had only drifted from the original 1918 virus, and thus they had developed partial immunity. The antibodies in young adults were specific for seasonal flu strains circulating since 1957. These were unable to protect them against the 2009 virus but may have formed damaging immune complexes with them. Youngsters had no anti-flu antibodies and did not form such immune complexes.

"Bird Flu"

Many influenza A viruses are found in birds, both domestic and wild. Most of these cause little or no illness in these hosts. However, some of their genes can enter viruses able to infect domestic animals, as was the case for the PA and PB2 genes of the swine flu of 2009 (above).

On several occasions, bird flu viruses have also infected humans, often with alarmingly-high fatality rates. In 2003, human cases of an H7N7 bird flu virus infection occurred in the Netherlands, and in the same year an H5N1 bird virus caused human cases in large areas of Asia. Most of the human cases seemed to have been acquired from contact with infected birds rather than from human-to-human transmission.

And now in 2013, a new bird flu virus, H7N9, has appeared in humans in China. By the end of the summer of 2013, it had caused 135 observed cases (no one knows yet whether there may also be infected people who are not sick enough to show up at hospitals). 45 of the observed cases were fatal. The victims appear to have been infected through contact with infected poultry with little or no evidence of human-to-human transmission.

As a glance at the tables above will show, humans have had long experience with infections and vaccines by both H1 and H3 flu viruses. But the human population has absolutely no immunity against any H7 viruses. If this virus develops the capability to spread efficiently from human to human, it could lead to another worldwide pandemic.


CDC Influenza Division

Daniel B. Jernigan, M.D., M.P.H., is the director of the Influenza Division in CDC&rsquos National Center for Immunization and Respiratory Diseases (NCIRD). Prior to his appointment, Dr. Jernigan served as deputy director of the Influenza Division from 2006 to 2014. As director, he is responsible for oversight and direction of the approximately 320 people working to reduce the domestic and global burden of disease and death due to seasonal, zoonotic and pandemic influenza. Dr. Jernigan also served as an officer in the U.S. Public Health Service. He retired as a Captain in 2019 after 23 years in the Commissioned Corps.

Dr. Jernigan received an undergraduate degree from Duke University, a Doctor of Medicine from Baylor College of Medicine, and a Master of Public Health from the University of Texas. He is board-certified in Internal Medicine and has completed an additional residency in Preventive Medicine.

Dr. Jernigan joined the CDC&rsquos Epidemic Intelligence Service in 1994 and worked in the Respiratory Diseases Branch on the prevention and control of bacterial respiratory pathogens. In 1996, he began serving on assignment from CDC to the Washington State Health Department as a medical epidemiologist and coordinator of national initiatives to improve surveillance for emerging infectious diseases. Dr. Jernigan became the chief of the Epidemiology Section in CDC&rsquos Division of Healthcare Quality Promotion (DHQP) in 2001. In that role, he supervised numerous investigations and initiatives to characterize various hospital-acquired, device-associated, and antimicrobial-resistant pathogen issues. In 2006, Dr. Jernigan joined the Influenza Division as Deputy Director.

Dr. Jernigan has authored more than 100 peer-reviewed articles and book chapters on various emerging infectious diseases topics, and has supervised outbreak investigations of viral, bacterial, and fungal infections associated with emerging and antimicrobial-resistant pathogens. He has led epidemiology and surveillance teams for national and international responses, including the 2001 bioterrorism-related anthrax, the 2002 emergence of West Nile virus, the 2003 SARS epidemic, 2009 H1N1 pandemic influenza, Ebola, and the 2019 COVID-19 pandemic. During the 2009 H1N1 influenza pandemic, Dr. Jernigan served as the CDC lead for all domestic and international epidemiology and laboratory activities for the U.S. government&rsquos response. In 2015, Dr. Jernigan served as the incident manager for the CDC&rsquos global Ebola response and in 2020 served as the incident manager for the CDC&rsquos COVID-19 domestic and global response.

Vivien G. Dugan, Ph.D., currently serves as the deputy director of the Influenza Division in CDC&rsquos National Center for Immunization and Respiratory Diseases (NCIRD). Dr. Dugan works closely with the division director to provide programmatic leadership and overall scientific and administrative management of the Influenza Division&rsquos activities and functions. She oversees the synchronization of epidemiologic and laboratory science with informatics and coordinates innovative intramural and extramural projects to advance the division&rsquos mission. Dr. Dugan served as acting director of the Influenza Division for six months in 2020 during CDC&rsquos COVID-19 response. Prior to her appointment in 2020, Dr. Dugan served as the deputy branch chief of the Virology, Surveillance and Diagnosis Branch (VSDB) in the Influenza Division.

Dr. Dugan earned a B.S. in Biology from Union College, an M.S. in Veterinary Parasitology, and a Ph.D. in Infectious Diseases from the College of Veterinary Medicine, University of Georgia, where she specialized in zoonotic, tick-borne pathogens. She studied avian influenza genomics as an NIH-funded postdoctoral fellow at The Institute for Genomic Research and the Armed Forces Institute of Pathology. Dr. Dugan completed her training on influenza virology and the evolution of pandemic and avian influenza viruses, including the 1918 and 2009 H1N1 pandemic viruses, at the Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), NIH.

Prior to joining CDC in 2016, Dr. Dugan was a program officer in the Office of Genomics and Advanced Technologies, Division of Microbiology and Infectious Diseases, NIAID, NIH. She provided leadership and scientific guidance for extramural research for controlling and preventing infectious diseases. This included functional genomics and systems biology approaches to study antimicrobial resistance, MERS and SARS coronaviruses, influenza viruses, and Ebola and Zika viruses. Dr. Dugan was an assistant professor of viral genomics at the J. Craig Venter Institute from 2010 to 2012, where she focused on influenza and vector-borne viral genomics, viral evolution and synthetic influenza vaccine development.

Eric Gogstad, M.Ed., is the associate director for program management for the Influenza Division in CDC&rsquos National Center for Immunization and Respiratory Diseases (NCIRD). Currently, he is responsible for program development, management and operations of the Influenza Division, which focuses on surveillance, research, and laboratory diagnostics in the United States and internationally. Mr. Gogstad has worked at CDC for years in a variety of different areas, including epidemiology and laboratory training, disease detection, emergency preparedness, refugee health, influenza, emerging infections and parasitic diseases. His educational background is in Communications, Human Resources and Organizational Development. Mr. Gogstad earned a B.S. in Administration from California State University, Chico and a Master of Education (M.Ed.) from the University of Georgia.

Mr. Gogstad has worked on global health with a focus on building public health systems and capacity within host governments around the world. Previously, he has been involved with various public and global health programs, including the International Emerging Infections Field Epidemiology and Laboratory Training Influenza Refugee Health Laboratory Systems Integrated Human and Animal Health and Emergency Preparedness and Response. In addition, Mr. Gogstad has collaborated with multi-lateral organizations, such as the World Health Organization (WHO), and other United States Government agencies, including the Department of State (DOS), United States Agency for International Development (USAID), and the Department of Defense (DOD).

Alicia M. Fry M.D., M.P.H., is the chief of CDC Influenza Division&rsquos Epidemiology and Prevention Branch. Dr. Fry is also a captain in the U.S. Public Health Service. As branch chief, she is responsible for oversight of a large domestic and international program that includes: influenza surveillance studies of the annual effects of influenza vaccines disease burden risk factors for severe disease forecasting and modeling efforts vaccine and antiviral guidance and policies outbreak investigations for seasonal influenza viruses and novel influenza A viruses capacity building, and pandemic preparedness and response.

Dr. Fry earned an undergraduate degree from the University of Connecticut, a Doctor of Medicine from the University of Cincinnati College of Medicine, and a Master of Public Health from the University of California, Berkeley. She trained in Internal Medicine at Johns Hopkins Hospital in Baltimore and Infectious Diseases at the University of California, San Francisco, and is board certified in Infectious Diseases.

Dr. Fry joined the CDC&rsquos Epidemic Intelligence Service in 1999, when she began work in the Respiratory Diseases Branch on the prevention and control of bacterial respiratory pathogens. In 2001, she worked in the International Tuberculosis Activities Branch to improve control of multidrug resistant tuberculosis. In 2002, Dr. Fry joined the outbreak team in the Foodborne and Diarrheal Diseases Branch. In 2004, she became lead of the Respiratory and Enterovirus team, where she characterized the epidemiology of respiratory syncytial viruses, parainfluenza viruses, human rhinoviruses, and human coronaviruses. She joined the Influenza Division in 2006 and, in 2012, she became the lead of the Influenza Prevention and Control team, where she advanced knowledge of vaccine and antiviral drug effects. In 2017, she became chief of the Epidemiology and Prevention Branch.

Dr. Fry has authored more than 200 peer-reviewed articles on various emerging infectious diseases topics. She has led epidemiology and medical counter measure teams for national and international responses, including 2009 H1N1 pandemic influenza, Cholera, Ebola, and the 2019 COVID-19 pandemic.

Joseph Bresee, M.D., is Influenza Division&rsquos associate director of global health affairs. Dr. Bresee also serves as director of the Partnership for Influenza Vaccine Introduction, based at the Task Force for Global Health, which seeks to accelerate the use of influenza vaccines in low and middle-income countries through public-private partnerships. He is the director of the Global Funders Consortium for Universal Influenza Vaccine Development, which provides a mechanism for global funders and stakeholders involved in next generation vaccine development to share strategies and lesson to accelerate progress in the field.

Dr. Bresee trained at Baylor College of Medicine in Houston, and then completed his Pediatric Residency at Children&rsquos Hospital and Medical Center at the University of Washington in Seattle. Dr. Bresee joined CDC in 1993 as an Epidemic Intelligence Service (EIS) officer in the Influenza Branch. From 1995 to 2005, Dr. Bresee first served as a staff epidemiologist and medical officer, specializing in viral gastrointestinal infections and respiratory infections. He was chief of CDC Influenza Division&rsquos Epidemiology and Prevention Branch from 2005-2017, overseeing a broad portfolio of global and domestic surveillance, research and policy activities for the Influenza Division. Dr. Bresee served as an officer in the U.S. Public Health Service. He retired as a Captain in 2017, after 24 years in the Commissioned Corps.

Dr. Bresee has authored more than 300 peer-reviewed papers and textbook chapters.

Terrence M. Tumpey, Ph.D., serves as chief of the Immunology and Pathogenesis Branch in CDC&rsquos Influenza Division. The Immunology and Pathogenesis Branch is internationally renowned for research on the pathogenesis, immunity and transmission of seasonal and pandemic influenza viruses &mdash specifically in the area of human infection with novel influenza viruses of animal origin. The branch also provides laboratory support for sero-epidemiological investigations of influenza infections in humans.

Dr. Tumpey earned his Bachelor of Arts degree in biology from the University of Minnesota and his Ph.D. in Microbiology/Immunology from the University of South Alabama School of Medicine in Mobile, Alabama. He was a recipient of the American Society for Microbiology (ASM) Postdoctoral Fellowship award and conducted his postdoctoral training in CDC&rsquos Influenza Branch. He later served the U.S. Department of Agriculture (USDA) as a Microbiologist at the Southeast Poultry Research Laboratory in Athens, Georgia. Dr. Tumpey rejoined the CDC in 2003 and became the team leader of pathogenesis, a position that required him to supervise eight microbiologists.

Dr. Tumpey&rsquos interests lie in elucidating the molecular determinants of virulence and transmission of influenza viruses, including pandemic influenza subtypes. He also contributes to the evaluation of influenza vaccines in a pre-clinical setting. In addition to his role at the CDC, Dr. Tumpey has an adjunct appointment at Atlanta&rsquos Emory University in the Department of Microbiology and Molecular Genetics. His research on pathogenesis and immunity during the last 30 years is documented in over 250 total peer-reviewed publications. In 2006, he was honored with the Lancet Award for the top scientific paper of 2005. He also received the 2006 and 2008 Charles C. Shepard awards for outstanding research papers. In 2007, Dr. Tumpey was inducted into the University of Minnesota, Duluth Academy of Science and Engineering, and he received the distinguished alumni award presented by the University of South Alabama.


Influenza Virus: Morphology and Its Replication | Microbiology

Influenza virus (Fig. 14.18) is pleomorphic and its diameter is 80- 120 nm. It is an enveloped virus possessing genome segmented into eight linear single- stranded molecules ranging in size from 890 to 2341 nucleotides. The nucleocapsid of this virus is of helical symmetry, about 6-9 nm in diameter and about 60 nm in length. The envelop contains outer lipid and inner protein layers.

There are two types of spikes, hemagglutinin spikes (H-spikes) and neuraminidase spikes (N-spikes), present on the outside surface of the envelop.

These spikes are about 500 in number (N-spikes only about 100 per virion) and interact with the host cell surface. Hemagglutinin spikes (H-spikes) cause agglutination of red blood cells (RBCs). An important feature of the hemagglutinin of influenza virus is that antibody directed against it prevents the virus from infecting a cell.

Thus, antibody directed against the hemagglutinin neutralizes the virus, and this is the mechanism by which immunity to influenza is brought about during immunization process. However, neuraminidase spike is an enzyme which breaks down the sialic acid component of the cytoplasmic membrane. On the inner side of the envelop there is M-protein which provides rigidness and thus stabilizes the lipid bilayer.

Replication of Influenza Virus:

Influenza virion enters inside the host cell by the process of endocytosis. There in the cytoplasm the nucleocapsid separates from the envelop and moves into the nucleus wherein the viral genome replication takes place. Un-coating results in activation of the virus RNA polymerase. The mRNA molecules are then transcribed from the virus RNA inside the nucleus using oligonucleotide primers and they move to the cytoplasm.

However, the virus proteins are synthesized in the cytoplasm. Ten virus proteins are encoded by the eight segments of viral genome. Some of these proteins are involved in viral genome replication while others are structural proteins used in assembly of virion. Details of assembly of virions are still not known with certainty. The formation of the complete enveloped progeny virion takes place by budding process.


Bacterial Exoenzymes and Toxins as Virulence Factors

​After exposure and adhesion, the next step in pathogenesis is invasion, which can involve enzymes and toxins. Many pathogens achieve invasion by entering the bloodstream, an effective means of dissemination because blood vessels pass close to every cell in the body. The downside of this mechanism of dispersal is that the blood also includes numerous elements of the immune system. Various terms ending in –emia are used to describe the presence of pathogens in the bloodstream. The presence of bacteria in blood is called bacteremia. Bacteremia involving pyogens (pus-forming bacteria) is called pyemia. When viruses are found in the blood, it is called viremia. The term toxemia describes the condition when toxins are found in the blood. If bacteria are both present and multiplying in the blood, this condition is called septicemia.

Patients with septicemia are described as septic, which can lead to shock, a life-threatening decrease in blood pressure (systolic pressure <90 mm Hg) that prevents cells and organs from receiving enough oxygen and nutrients. Some bacteria can cause shock through the release of toxins (virulence factors that can cause tissue damage) and lead to low blood pressure. Gram-negative bacteria are engulfed by immune system phagocytes, which then release tumor necrosis factor, a molecule involved in inflammation and fever. Tumor necrosis factor binds to blood capillaries to increase their permeability, allowing fluids to pass out of blood vessels and into tissues, causing swelling, or edema (Figure 1). With high concentrations of tumor necrosis factor, the inflammatory reaction is severe and enough fluid is lost from the circulatory system that blood pressure decreases to dangerously low levels. This can have dire consequences because the heart, lungs, and kidneys rely on normal blood pressure for proper function thus, multi-organ failure, shock, and death can occur.

Figure 1. ​This patient has edema in the tissue of the right hand. Such swelling can occur when bacteria cause the release of pro-inflammatory molecules from immune cells and these molecules cause an increased permeability of blood vessels, allowing fluid to escape the bloodstream and enter tissue.

Influenza Basic Research

NIAID has a longstanding commitment to conducting and supporting the basic research necessary to understand how influenza strains emerge, evolve, infect and cause disease (called pathogenesis) in animals and humans. Results from this research are used to inform the design of new and improved influenza vaccines, diagnostics and antiviral drugs to treat flu infection.

Influenza is challenging for scientists to study because there are hundreds of strains that are classified into four main categories: A through D, though D is not known to infect people. Influenza A virus is the group that most commonly causes illness in humans and is the source of all of the major influenza pandemics in modern history. This type can drift and shift through birds and animals, meaning it emerges with rearranged surface proteins that create different strains of the virus.

The surface proteins that combine in different ways to create an assortment of influenza virus type A strains are called hemagglutinin (HA) and neuraminidase (NA). Hemagglutinin enables the flu virus to enter a human cell and initiate infection neuraminidase allows newly formed flu viruses to exit the host cell and multiply throughout the body. There are 18 types of HA and 11 types of NA, leaving the possibility for dozens of different subtypes of influenza A viruses (such as H1N1, H3N2, H5N8, and H7N9) and strains (such as 1918 H1N1 influenza and 2009 H1N1 flu).

Some of the specific questions about influenza that basic science researchers explore include how strains of viruses differ from each other by gene structure how viruses can defeat the immune system to cause disease how some viruses can transmit from person to person and how some treatments and vaccines effectively prevent or minimize infection.


Antigenic shift

Our editors will review what you’ve submitted and determine whether to revise the article.

Antigenic shift, genetic alteration occurring in an infectious agent that causes a dramatic change in a protein called an antigen, which stimulates the production of antibodies by the immune systems of humans and other animals. Antigenic shift has been studied most extensively in influenza type A viruses, which experience this change about once every 10 years. The newly emerged viruses have the potential to cause epidemics or pandemics, since very few, if any, humans possess immunity against the new antigens.

Antigenic shift occurs because influenza A viruses have a large animal reservoir, consisting primarily of wild aquatic birds (e.g., ducks). It also occurs because the RNA genome of influenza A viruses is in the form of eight segments, which during viral replication are susceptible to a type of genetic exchange known as genetic reassortment. Reassortment can result in antigenic shift when an intermediate host, such as a pig, is simultaneously infected with a human and an avian influenza A virus. The new version of the virus that is produced represents a new influenza A subtype and thus is immunologically distinct from influenza A viruses that have been circulating in the human population. Influenza A subtypes are distinguished by the two major antigenic glycoproteins, hemagglutinin (H) and neuraminidase (N), that exist on their viral coats. (H1N1, H3N2, and H5N1 are examples of influenza A subtypes.)

Antigenic shift may also occur when an influenza A virus jumps directly from aquatic birds to humans or when a virus passes from aquatic birds to humans through an intermediate host without undergoing reassortment.

This article was most recently revised and updated by Kara Rogers, Senior Editor.


Coronavirus is a positive-sense single-stranded RNA virus which causes illnesses ranging from common cold and pneumonia to severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS). In contrast, influenza virus is a negative-sense, single-stranded RNA virus which causes seasonal flu epidemics each year. So, this is the key difference between coronavirus and influenza. Moreover, coronavirus spread slowly while the influenza virus spreads rapidly than the coronavirus. Furthermore, coronavirus infections are more deadly than influenza virus infections. Most importantly, there is no vaccine for coronavirus yet while there is a vaccine for the influenza virus.

The below info-graphic summarizes the difference between coronavirus and influenza.


Archival influenza virus genomes from Europe reveal genomic and phenotypic variability during the 1918 pandemic

The 1918 influenza pandemic was the deadliest respiratory pandemic of the 20th century and determined the genomic make-up of subsequent human influenza A viruses (IAV). Here, we analyze the first 1918 IAV genomes from Europe and from the first, milder wave of the pandemic. 1918 IAV genomic diversity is consistent with local transmission and frequent long-distance dispersal events and in vitro polymerase characterization suggests potential phenotypic variability. Comparison of first and second wave genomes shows variation at two sites in the nucleoprotein gene associated with resistance to host antiviral response, pointing at a possible adaptation of 1918 IAV to humans. Finally, phylogenetic estimates based on extended molecular clock modelling suggests a pure pandemic descent of seasonal H1N1 IAV as an alternative to the hypothesis of an intrasubtype reassortment origin.

One Sentence Summary Much can be learned about past pandemics by uncovering their footprints in medical archives, which we here demonstrate for the 1918 flu pandemic.


Avian biology, the human influence on global avian influenza transmission, and performing surveillance in wild birds

This paper takes a closer look at three interrelated areas of study: avian host biology, the role of human activities in virus transmission, and the surveillance activities centered on avian influenza in wild birds. There are few ecosystems in which birds are not found. Correspondingly, avian influenza viruses are equally global in distribution, relying on competent avian hosts. The immune systems, annual cycles, feeding behaviors, and migration patterns of these hosts influence the ecology of the disease. Decreased biodiversity has also been linked to heightened disease transmission in several disease systems, and it is evident that active destruction and modification of wetland environments for human use is impacting avian populations drastically. Legal and illegal trade in wild birds present a significant risk for introduction and maintenance of exotic diseases. After the emergence of HPAI H5N1 in Hong Kong in 1996 and the ensuing geographic spread of outbreaks after 2003, both infected countries and those at risk of introduction began intensifying avian influenza surveillance efforts. Several techniques for sampling wild birds for influenza viruses have been applied. Benefits, problems, and biases exist for each method. The wild bird avian influenza surveillance programs taking place across the continents are now scaling back due to the rise of other spending priorities hopefully the lessons learned from this work will be preserved and will inform future research and disease outbreak response priorities.


"Bird Flu"

Many influenza A viruses are found in birds, both domestic and wild. Most of these cause little or no illness in these hosts. However, some of their genes can enter viruses able to infect domestic animals, as was the case for the PA and PB2 genes of the swine flu of 2009 (above).

On several occasions, bird flu viruses have also infected humans, often with alarmingly-high fatality rates. In 2003, human cases of an H7N7 bird flu virus infection occurred in the Netherlands, and in the same year an H5N1 bird virus caused human cases in large areas of Asia. Most of the human cases seemed to have been acquired from contact with infected birds rather than from human-to-human transmission.

And now in 2013, a new bird flu virus, H7N9, has appeared in humans in China. By the end of the summer of 2013, it had caused 135 observed cases (no one knows yet whether there may also be infected people who are not sick enough to show up at hospitals). 45 of the observed cases were fatal. The victims appear to have been infected through contact with infected poultry with little or no evidence of human-to-human transmission.

As a glance at the tables above will show, humans have had long experience with infections and vaccines by both H1 and H3 flu viruses. But the human population has absolutely no immunity against any H7 viruses. If this virus develops the capability to spread efficiently from human to human, it could lead to another worldwide pandemic.


Watch the video: Συμβουλές για να νικήσετε τη γρίπη και τις ιώσεις (January 2022).