Molecular Features of Highly Pathogenic Avian and Human H5N1 Influenza A Viruses in Asia

The highly pathogenic avian H5N1 influenza virus could infect humans with high mortality rate, even though it has not yet become efficiently transmissible among humans. This proteomic study investigated the molecular basis of interspecies transmission and host range of this lethal virus in Asia, due to its potential pandemic threat. Although there are host markers located in previous research between general avian and human influenza viruses, the novelty of our work was to uncover host markers between highly pathogenic avian and human H5N1 viruses in Asia. Many host markers we found were not present in the previous general markers, thus expanding the current repertoire of host markers with these strain-specific host markers. Ranked by their order of importance, the top 10 host markers discovered in this report were PB2_627, HA_325, NS1_205, PB2_524, HA_86, NA_201, NP_373, NS1_7, HA_156, NA_74, confirming our current knowledge that PB2_627 is the most critical site for distinguishing avian and human H5N1. We also identified several naturally-occurred mutations in the HA protein that might shift the receptor binding preference of Asian avian H5N1, since early detection of mutations that might lead to emergence of a new pandemic virus is of prime importance. Finally, we analyzed the distinctive interaction patterns within and between proteins of avian and human H5N1 in Asia at protein level and individual residue level. From multiple viewpoints, our findings reinforced the experimental observation that multiple genes of Asian avian H5N1 are involved in its gradual adaptation to human hosts.