Q&A: What have we found out about the influenza A (H1N1) 2009 pandemic virus?

The 1918 pandemic influenza virus is said to have started by causing relatively mild disease in the summer but to have become more severe in the winter. Do we know why, and might influenza A (H1N1) 2009 do the same? It is not clear precisely what changes resulted in the increased severity of infection during the second wave of the 1918 Spanish influenza pandemic. Certainly the occurrence of multiple waves of influenza infection in the same year is unusual and one possibility is progressive adaptation of the 1918 Spanish influenza virus to its new human host [1]. Molecular analysis, for example, suggests that the virus that emerged during the second wave in the Northern hemisphere had undergone changes in the hemagglutinin (HA) binding site that increased binding specificity for human receptors [2]. This is presumed to have affected the replicative capacity and, therefore, the pathogenicity of the virus. The 1918 Spanish influenza virus also encoded a non-structural 1 (NS1) protein capable of blocking interferon production and thus prevention of viral replication by the host [3]. Changes in the NS1 protein may also have contributed to host adaptation and increased virulence [1]. Importantly, however, two of the features that account for the virulence of the highly patho genic avian influenza A (H5N1) viruses are not present either in the Spanish influenza virus or in the current pandemic influenza A (H1N1) 2009 virus [4]. These are a lysine at position 627 of the polymerase basic subunit 2, and glutamic acid in position 92 of NS1 that, at least in animal models of infection, increase the replicative capacity of the virus and block host inhibition of viral replication, respectively [5,6]. As the (H1N1) 2009 pandemic virus continues to spread, the opportunities for adaptation that increases virulence in the human host also increase, but the changes required for such adaptation and for increased virulence are difficult to predict and by no means inevitable [7]. What about the possibility that influenza A (H1N1) might recombine with other more virulent viruses? There is some concern that co-circulation with seasonal influenza A viruses during the winter, or with highly pathogenic H5N1 viruses in countries where those viruses are endemic, might lead to the emergence of more virulent reassortant viruses [8]. But although occasional dual infections with pandemic and seasonal viruses have been detected during the 2009 Southern hemisphere winter, there have been no reports of emergence of …