Researchers at Pennsylvania State University and the National Institute of Health used an evolutionary analysis of influenza viruses sampled from 1918 “ 2005 to investigate the influenza viruses that cause seasonal epidemics in humans, particularly those where mortality was unusually high. Specifically, the researchers found that the severe influenza epidemics of 1947 and 1951 were caused by genetic reassortment events in which two human influenza viruses of the same H1N1 strain exchanged genetic material, producing a new hybrid virus in both cases.
It has been a mystery why unusually severe epidemics of influenza occur from time to time, such as in 1947 and 1951, when illness and mortality rates exceeded standard epidemic levels. The standard model of human influenza virus evolution holds that major influenza pandemics, the largest of which occurred in 1918, are caused by reassortment between human and avian influenza viruses. But seasonal influenza epidemics, which occur each winter in the United States, do not involve the reassortment of genetic material.
These new findings suggest that the evolution of seasonal influenza is more complex than previously thought, and that multiple forms of the same strain co-circulate and re-assort within a single population, rapidly generating genetically novel viruses with the potential to ignite major epidemics. It is therefore critical that intensive surveillance is undertaken to capture the full extent of influenza genetic diversity that co-circulates at a given time, particularly as an aid to vaccine design.
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Understanding how each strain evolves over time is crucial. H3N2 is the dominant strain and evolves much more rapidly than H1N1. So the H1N1 component of each year's flu vaccine has to be updated less often. In comparison, the H3N2 component of the vaccine has been changed four times over the past seven years.
Last year the infections were dominated by H1N1 but we had no way of predicting it, said Nelson. This year the vaccine failure is due to the H3N2 mismatch because researchers picked the wrong strain.
The H1N1 virus is particularly unusual because it disappeared completely in 1957, only to mysteriously re-emerge in humans in 1977 in exactly the same form in which it had left. It is still not certain what happened to the virus during its disappearance. But since it did not evolve at all over these twenty years, the only plausible explanation is that it was some kind of a lab escape, says Nelson, who is also affiliated with Penn State's Center for Infectious Disease Dynamics (CIDD).
In recent decades, flu infections in the United States have been dominated by yet another reassorted viral strain known as H3N2. This strain caused the Hong Kong flu pandemic of 1968, which killed nearly a million people.
The Penn State researcher says the study shows that the evolution of a virus is not limited to the mutation of single lineage, and that there are multiple strains co-circulating and exchanging genetic material. The H1N1 and H3N2 strains, for instance, are occasionally generating hybrid H1N2 viruses.
If we really want effective vaccines each year, our surveillance has to be much broader than simply looking at one lineage and its evolution, and trying to figure out how it is going to evolve by mutation, said Nelson. You have to look at a much bigger picture.
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