Genetic stability and linkage analysis of the 2009 Influenza A(H1N1) virus based on sequence homology.

The 2009 swine-origin Influenza A virus subtype H1N1 (S-OIV) is generally believed to be a mixture of human, bird and swine viruses, resulting from multiple reassortments. The evolutionary origin of the S-OIV is of high interest but still remains obscure. In order to understand the evolution of the new virus, we performed sequence homology, segment stability and segment linkage analysis, as well as analysis of the host and geographic distribution of the evolutionarily related viruses. Stability analysis demonstrated that segment 6 (NA) was the most unstable one, followed by segment 4 (HA), while the other 6 segments were relatively stable. Host and geographic distribution analysis indicated that all 8 segments of the new virus were closely related to those of swine influenza viruses circulating either in North America or in Eurasia. Segment linkage analysis showed that segments 1 (PB2), 2 (PB1), 3 (PA), 4 (HA), 5 (NP), and 8 (NS) are in linkage disequilibrium exclusively with North American swine influenza viruses, and segments 6 (NA) and 7 (M) are evolutionarily linked solely with Eurasian swine influenza viruses. Two North American swine strains and 2 Eurasian swine strains were identified as possible ancestors of S-OIV 2009. Based on the most recent linkage analysis with the updated influenza sequences, South Dakota avian strains were found to be the closest known relatives of S-OIV 2009.