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The interpandemic evolution of the influenza A virus hemagglutinin (HA) protein is commonly considered a paragon of rapid evolutionary change under positive selection in which amino acid replacements are fixed by virtue of their effect on antigenicity, enabling the virus to evade immune surveillance.We performed phylogenetic analyses of the recently obtained large and relatively unbiased samples of the HA sequences from 1995–2005 isolates of the H3N2 and H1N1 subtypes of influenza A virus.
In 1977, the H1N1 subtype reappeared, albeit with a lower virulence than both the original H1N1 of the 1918–1956 period and the H3N2 subtype, and since then has been co-circulating with H3N2 , demonstrating the epidemiological significance of this phenomenon.These observations have implications for influenza surveillance and vaccine formulation; in particular, the possibility exists that parallel amino acid replacements could serve as a predictor of new dominant strains. Unlike most pathogens where exposure leads to lasting immunity in the host, influenza A virus presents a moving antigenic target, evading specific immunity triggered by previous infections. Antigenic shift occurs when the virus acquires an HA of a different influenza subtype via reassortment of one or more gene segments and is thought to be the basis for the more devastating influenza pandemics that occurred several times in the last century.There have been three pandemics in the last hundred years: in 1918 (H1N1 subtype), 1957 (H2N2 subtype), and in 1968 (H3N2 subtype).A number of parallel amino acid replacements – the same amino acid substitution occurring independently in different lineages – were also detected in H3N2 HA.