Evolutionary dynamics of the influenza A pandemic (H1N1) 2009 virus with emphasis on Indian isolates: evidence for adaptive evolution in the HA gene

The indigenous transmission of the 2009 pandemic H1N1 (pH1N1) virus in India made it as one of the major sub-types in circulation. Genetic characterization indicated that the viruses predominantly clustered in clade 7, the globally most widely circulating pH1N1 clade. It is imperative to continue monitoring the genetic make-up of the pH1N1 viruses to understand their adaptability and evolutionary dynamics in the country. We characterized 31 full genomes and 94 hemagglutinin (HA) sequences of the pH1N1 viruses from various regions of India (May 2009-October 2010). Among the newly identified mutations reported in the pH1N1 viruses that could alter the viral fitness, E374K in the HA was increasingly noted in 35 Indian isolates beyond September 2009 and its co-occurrence with D97N or V30A was also observed in the more recent isolates. Molecular clock analysis based on all Indian isolates and closely related global representatives indicated higher substitution rates (∼ 7.1 × 10(-3) subs/site/year) when compared to an earlier report. Several independent introductions were noted within the country along with considerable evidence of indigenous evolution during the latter period of the study. The estimate for the mean age of the common ancestor of all the pandemic isolates dated to around August 2008 correlating well with the global estimate. Evidence for adaptive evolution in the HA was observed in the clade 7 isolates at the 'Ca' antigenic site that may have implications for future re-evaluation of the vaccine composition. The study thus warrants the need for continued surveillance and genetic characterization of whole genome sequences to detect any possible reassortment events that might further contribute to the viral fitness of the pH1N1 viruses.