Live Poultry Trading Drives China's H7N9 Viral Evolution and Geographical Network Propagation.

The on-going reassortment, human-adapted mutations, and spillover events of novel A(H7N9) avian influenza viruses pose a significant challenge to public health in China and globally. However, our understanding of the factors that disseminate the viruses and drive their geographic distributions is limited. We applied phylogenic analysis to examine the inter-subtype interactions between H7N9 viruses and the closest H9N2 lineages in China during 2010-2014. We reconstructed and compared the inter-provincial live poultry trading and viral propagation network via phylogeographic approach and network similarity technique. The substitution rates of the isolated viruses in live poultry markets and the characteristics of localized viral evolution were also evaluated. We discovered that viral propagation was geographically-structured and followed the live poultry trading network in China, with distinct north-to-east paths of spread and circular transmission between eastern and southern regions. The epicenter of H7N9 has moved from the Shanghai-Zhejiang region to Guangdong Province was also identified. Besides, higher substitution rate was observed among isolates sampled from live poultry markets, especially for those H7N9 viruses. Live poultry trading in China may have driven the network-structured expansion of the novel H7N9 viruses. From this perspective, long-distance geographic expansion of H7N9 were dominated by live poultry movements, while at local scales, diffusion was facilitated by live poultry markets with highly-evolved viruses.