|MadSci Network: Virology|
Question: How exactly does influenza evolve into new strains so often?
Influenza virus has a number of factors going for it in regards to its ability to evolve into new strains.
The modern history of influenza began with its isolation from humans in 1933. This virus was later shown to be antigenically related to a virus isolated in swine two years earlier. In 1940, a second antigenically distinct human virus was isolated and it was designated influenza B, to distinguish it from the earlier virus which was then designated influenza A. Finally, a third antigenically distinct virus, influenza C virus, was isolated in 1949. We will concentrate on influenza A & B viruses in this lecture.
Influenza A viruses are classified and divided into subtypes based on their surface glycoprotein antigens: 14 subtypes of hemagglutinin (HA or H) H1-H14 and 9 types of neuraminidase (NA or N) N1-N9. These influenza type A viruses are able to infect a number of different species including: humans, swine, horses birds, and aquatic mammals. All 14 subtypes of HA have been isolated from birds, 3 of them in humans, two in pigs, horses, seals and whales, and one in mink. The NA antigens show a similar species distribution. Therefore, a large number of non-crossreactive influenza antigens are always circulating in nature. Antibodies produced against HA and NA antigens are responsible for protection against re-infection by the identical virus subtype.
Major evolutionary changes (emergence of new viruses) in the influenza type A viruses occur by the mixing or re-assorting of their genetic material causing changes in their external surface HA and NA antigens. This phenomenon is known as “antigenic shift.” The genetic material or genomes of influenza viruses occur in eight separate molecules or segments. If two different subtypes of influenza A virus infect the same cell, their genetic segments are able to reassort and produce a new influenza virus with segments from both infecting viruses. As an example, if a H3N5 virus and a H2N2 virus infect the same cell the following offspring viruses can be produced: H3N5, H2N2, H3N2, and H2N5. This re- assortment can occur between human and animal isolates. Therefore, new viruses can be produced which can replicate in humans, but have new subtypes of animal HA and NA antigens. There are no protective antibodies to these antigens in the human population, so the new virus can spread very rapidly around the world.
The virus subtypes that have been so far been known to infect humans are H1N1, H2N2, and H3N2. The H1N1 viruses circulated from the beginning of the century through the 1950’s. In 1957, a new H2N2 virus appeared, known as the “Asian Flu”, and rapidly spread around the world. This virus had both a new HA and a new NA. In 1968, another new virus appeared – a H3N2 virus, known as the “Hong Kong Flu.” This virus was not as severe as the H2N2 virus, since it only varied in the HA antigen. The H1N1 virus also reappeared in 1977. Currently, both the H3N2 and H1N1 viruses are circulating through the human population. The major question is what new virus (H?N?) will emerge in the future and cause the next major world-wide epidemic.
You may then ask, “Why then do people get sick with the flu every couple of years, when there has been no major change in the HA or NA antigens?”
Well, between major changes in the HA and NA antigens, point mutations can occur on the HA and NA molecules and these mutations may help the virus to avoid the protective antibodies and produce an illness. This phenomenon is known as “antigenic drift.” The H3N2 virus has been able to successfully drift from its initial appearance in 1968 and still produce infections in 1999.
Additional information about influenza viruses and their evolution can be found at the following websites:
The views and opinions expressed here are my own and may not reflect those of my employer.
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