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The "Flu"

Influenza is a viral infection of the lungs characterized by fever, cough, and severe muscle aches. In the elderly and infirm, it is a major cause of disability and death (often as a result of secondary infection of the lungs by bacteria). Even in the young and healthy, influenza produces a prostrating disease of a few days duration and one not soon forgotten.

Influenza is not 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 bt="285" align="right">

This electron micrelow).

There are three types of influenza:

The Influenza A Virus

The influenza A virion is Each of the 8 RNA molecules is associated with Each of the 8 RNA molecules is associated with

The Genes of Influenza A

The 8 RNA molecules (the number in brackets is the designated segment number):

The Disease

The influenza virus invades cells of the respiratory passages.

The result/a> (mRNA) molecules to be translated into the proteins of fresh virus particles.

  • Fresh virus buds off from the plasma membrane of the cell (aided 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 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 strains of influenza A
    DateStrainSubtypeNotes
    1918H1N1pandemic of "Spanish" flu
    1957A/Singapore/57H2N2pandemic of "Asian" fluDateStrainSubtypeNotes
    1918H1N1pandemic of "Spantd>
    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 add 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 beenults. 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: