Glycosylation patterns of surface proteins in ecology and evolution of influenza H1N1 viruses

Abstract

The highly variable nature of influenza viral genome presents an effective way to evade antibody-mediated neutralization. The N-linked glycosylation of two viral surface proteins, hemagglutinin (HA) and neuraminidase (NA), has been suggested an important factor that affect the virulence and antigenicity of the viruses. Here, I analyzed the potential N-glycosylations of the HA and NA of influenza H1N1 viruses isolated from human, avian, and swine species isolated for the past century. My analysis identified three major glycosylation clusters on the HA that are closely related with the evolution of influenza H1N1 viruses during pandemics and seasonal epidemics. Of note, the 1976 ‘abortive pandemic’ virus demonstrated similar glycosylation pattern to the H1N1 pandemic viruses in 1918 and 2009 in its complete absence of glycosylations in the all three clusters. Parallel analysis on the NA revealed a dramatic shift in glycosylation site as an independent hallmark for pandemics. The cosegregation of particular glycosylations in the HA and NA was identified as signature for zoonotic transmission from animal reservoirs, and interestingly, in ‘reverse zoonosis’ of human viruses into swine population as well. In silico prediction indicated the pleiotropic influence of glycans on multiple epitopes of the HA without sacrificing viral fitness for human infection. The cosegregational and counter-balanced glycosylations on the HA and NA could be implemented in influenza surveillance for better prediction of pandemics and for improving influenza vaccines.