Functional Interplay between Hemagglutinin and Neuraminidase of Pandemic 2009 H1N1 from the Perspective of Virus Evolution

Influenza type A viruses are classified into subtypes based on their two surface proteins, hemagglutinin (HA) and neuraminidase (NA). Our time series analysis on the strains of pandemic 2009 H1N1 collected from 2009 to 2013 demonstrated that the HA receptor binding preference of this virus in USA, Europe, and Asia has been the characteristic of swine H1N1 virus since 2009. However, its binding characteristics of seasonal human H1N1 and avian H1N1 both have been on steady rise with American strains having the sharpest surge in 2013. The first increase could enhance the viral transmission and replication in humans and the second boost its ability to cause infection deep in lungs, which might explain the recent human deaths caused by this virus in Texas in December 2013. We further explored the corresponding NA activity of this virus to reveal the functional interdependence between HA and NA during the evolution and adaptation of this virus from 2009 to 2013. To understand the real causality, the amino acid substitutions in HA and NA that actually produced the mutations were also identified.