Evolution of influenza A(H7N9) viruses from waves I to IV

The H7N9 influenza virus that emerged in East China in early 2013 has caused 736 human infections with a fatality rate of 38.5%, through four outbreak waves. Our previous studies revealed that this virus was generated by reassortment between viruses from wild bird H7 and N9 viruses (surface genes) and poultry H9N2 viruses (internal genes), and that while the H7N9 wave I viruses had highly similar surface genes, the surface genes of the wave II viruses developed into regionally distinct clades. The H7N9 viruses continued to reassort with different H9N2 viruses to obtain internal gene segments, thereby generating multiple variants or genotypes. Our ongoing surveillance suggests that the H7N9 virus has become enzootic in chickens, and disseminated to most regions of China during waves III and IV of the outbreak. In this study, we have generated more than 800 H7N9 virus full genome sequences, and are analyzing these together with all genomes available in public databases. We are exploring the following scientific questions: (i) what is the continuing evolutionary behavior of the H7N9 virus lineage; (ii) what are the interactions or gene transfers between circulating H7N9 viruses and other enzootic influenza viruses, and the changes in genotypes over the four waves; (iii) what are the interactions among sub-lineages or clades, i.e. predominance and/or sub-lineage replacement; and (iv) what is the development and dissemination of the H7N9 viruses from a phylogeographic perspective. We hope that the information generated by this project will provide insights into methods to manage the development of the H7N9 outbreak and help to avert similar situations from arising.published_or_final_versio