Research Article: Evolutionary Trends of A(H1N1) Influenza Virus Hemagglutinin Since 1918

Date Published: November 17, 2009

Publisher: Public Library of Science

Author(s): Jun Shen, Jianpeng Ma, Qinghua Wang, Darren P. Martin.

Abstract: The Pandemic (H1N1) 2009 is spreading to numerous countries and causing many human deaths. Although the symptoms in humans are mild at present, fears are that further mutations in the virus could lead to a potentially more dangerous outbreak in subsequent months. As the primary immunity-eliciting antigen, hemagglutinin (HA) is the major agent for host-driven antigenic drift in A(H3N2) virus. However, whether and how the evolution of HA is influenced by existing immunity is poorly understood for A(H1N1). Here, by analyzing hundreds of A(H1N1) HA sequences since 1918, we show the first evidence that host selections are indeed present in A(H1N1) HAs. Among a subgroup of human A(H1N1) HAs between 1918∼2008, we found strong diversifying (positive) selection at HA1 156 and 190. We also analyzed the evolutionary trends at HA1 190 and 225 that are critical determinants for receptor-binding specificity of A(H1N1) HA. Different A(H1N1) viruses appeared to favor one of these two sites in host-driven antigenic drift: epidemic A(H1N1) HAs favor HA1 190 while the 1918 pandemic and swine HAs favor HA1 225. Thus, our results highlight the urgency to understand the interplay between antigenic drift and receptor binding in HA evolution, and provide molecular signatures for monitoring future antigenically drifted 2009 pandemic and seasonal A(H1N1) influenza viruses.

Partial Text: Since April 2009, a global outbreak caused by the swine-origin 2009 A(H1N1) influenza virus has spread to numerous countries [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], which warranted the declaration of “Pandemic (H1N1) 2009” by the World Health Organization on June 11, 2009. As of September 6, there had been over 277,607 infected individuals and at least 3,205 confirmed human deaths worldwide.



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