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Computational Study of Interdependence Between Hemagglutinin and Neuraminidase of Pandemic 2009 H1N1

tetano

Editor, Senior Moderator
IEEE Trans Nanobioscience. 2015 Mar 2. [Epub ahead of print]
[h=1]Computational Study of Interdependence Between Hemagglutinin and Neuraminidase of Pandemic 2009 H1N1.[/h] Hu W.
[h=3]Abstract[/h] Influenza type A viruses are classified into subtypes based on their two surface proteins, hemagglutinin (HA) and neuraminidase (NA). The HA protein facilitates the viral binding and entering a host cell and the NA protein helps the release of viral progeny from the infected cell. The complementary roles of HA and NA entail their collaboration, which has important implications for viral replication and fitness. The HA protein from early strains of pandemic 2009 H1N1 of swine origin preferentially binds to human type receptors with a weak binding to avian type receptors. This virus caused several human deaths in De-cember 2013 in Texas USA, which motivated us to investigate the changes of genetic features that might contribute to the surged virulence of the virus. Our time series analysis on the strains of this virus col-lected from 2009 to 2013 implied that the HA binding preference of this virus in USA, Europe, and Asia has been the characteristic of swine H1N1 virus since 2009. However, its characteristic of seasonal hu-man H1N1 and its binding avidity for avian type receptors both were on steady rise and had a clear in-crease in 2013 with American strains having the sharpest surge. The first change could enhance the viral transmission and replication in humans and the second could increase its ability to cause infection deep in lungs, which might account for the recent human deaths in Texas. In light of HA and NA coadaptation and evolutionary interactions, we also explored the NA activity of this virus to reveal the functional bal-ance between HA and NA during the course of virus evolution. Finally we identified amino acid substitu-tions in HA and NA of the virus that were critical for the observed evolution.


PMID: 25751873 [PubMed - as supplied by publisher]
 
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