Comprehensive sequence analysis of HA protein of H7 subtype avian influenza viruses: an emphasis on mutations in novel H7N9 viruses

Aim: H7 avian influenza viruses pose a major public health threat raising concerns regarding their pandemic potential, especially after the recent outbreak in China of H7N9 subtype viruses. The objective was to gain insight into the geographical and host-wise distribution of H7 subtype viruses, and to understand molecular determinants responsible for their adaptation in humans. Materials & methods: In this study we carried out a global comprehensive analysis of 1749 HA sequences belonging to the H7 subtype available in the Global Initiative on Sharing All Influenza Data (GISAID) EpiFlu (TM) database. We also analyzed full-genome sequences of the 27 influenza strains belonging to the H7N9 subtype isolated recently from China. Results: Most of the H7 strains were from North America (749) followed by in Europe (659) and Asia (284). The majority of the sequences belonged to the H7N7 subtype (524) followed by H7N3 (440) and H7N2 (411), while 107 belonged to H7N9. Comparison of HA sequences of H7 viruses isolated from humans showed the presence of mutations and determinants that could have played a pivotal role in avian-to-human transmission and adaptability in humans. Mutational analysis of all the segments of the recent H7N9 viruses isolated from humans in China revealed that these viruses possessed several characteristic features of mammalian influenza viruses. Conclusion: H7 viruses, irrespective of being of high or low pathogenicity have a propensity to adapt to humans causing mild to severe infections. These viruses have signature mutations that have been associated with interspecies transmission and human adaptability, raising concerns regarding their pandemic potential.