Multiple amino acid mutations in viral RNA polymerase may synergistically enhance the transmissibility and/or virulence of the 2009 pandemic influenza (H1N1) virus.

Influenza viruses may change their transmissibility and virulence via single or multiple point mutations in the functional regions of their structural proteins. In this study, we compared sequences of all three subunits of viral RNA polymerase, i.e. PA, PB1 and PB2, of the 2009 pandemic influenza A (H1N1) virus isolates from different stages of the pandemic and found that the frequencies of three mutations, including V14I and K716Q in PA and K736G in PB1, showed a similar trend. Interestingly, the death rate of infected patients during the pandemic matched the frequency of the three mutations with a 2-months delay. These findings suggest that the combined mutations may have acted synergistically in enhancing the transmissibility and/or virulence of the 2009 pandemic virus. If definitely proved, this hypothesis could guide the rational design of antiviral therapeutics targeting the RNA polymerase of influenza viruses.