Tropism of pandemic 2009 H1N1 influenza A virus

Substitutions at the receptor-binding site of the pandemic H1N1 2009 influenza A virus (H1N1pdm) hemagglutinin (HA) gene may be critical in determining whether a virus binds to human or avian receptors. Previous reports suggest that HA GIy(222) and/or Arg(223) allow viruses to bind preferentially to the alpha 2,3-linked sialic acid found in avian species. We also demonstrated that serial passaging of influenza A virus in embryonated chicken eggs increased viral growth 32- to 64-fold, coincident with the increased prevalence of GIy(222) or Arg(223) in HA protein (Yasugi et al., 2012). In this study, we showed that the minor genotype of alpha 2,3-linkage-tropic viruses in upper airways became dominant after passaging through chicken eggs. Viruses possessing HA containing N125D-Q223R, N125D-D187E-Q223R, K119N-D222G, and K119N-N1295-D222G, were detected in both clinical specimens and egg-passaged samples. These results might suggest that egg-adapted viruses, likely represented by alpha 2,3-linkage-tropic virus, were also present in human upper airways as a minor population and transmitted in humans during the outbreak of H1N1pdm.