Comparative Co-Evolution Analysis Between the HA and NA Genes of Influenza A Virus

Influenza A virus subtypes are determined based on envelope proteins encoded by the hemagglutinin (HA) gene and the neuraminidase (NA) gene, which are involved in attachment to the host, pathogenicity, and progeny production. Here, we evaluated such differences through co-evolution analysis between the HA and NA genes based on subtype and host. Event-based cophylogeny analysis revealed that humans had higher cospeciation values than avian. In particular, the yearly ML phylogenetic trees for the H1N1 and H3N2 subtypes in humans displayed similar topologies between the two genes in humans. Substitution analysis was verifying the strong positive correlation between the two genes in the H1N1 and H3N2 subtypes in humans compared with those in avian and swine. These results provided a proof of principle for the further development of vaccines according to hosts and subtypes against Influenza A virus.