Sustaining a Regional Emerging Infectious Disease Research Network: A Trust-Based Approach

Origin and diversity of novel avian influenza a H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses (H7N9 report)

Authors: Di Liu*, Weifeng Shi*, Yi Shi, Dayan Wang, Haixia Xiao, Wei Li, Yuhai Bi, Ying Wu, Xianbin Li, Jinghua Yan, Wenjun Liu, Guoping Zhao, Weizhong Yang, Yu Wang, Juncai Ma, Yuelong Shu†, Fumin Lei†, George F Gao†

Institution: Various Collaboration

Summary

Background On March 30, 2013, a novel avian influenza A H7N9 virus that infects human beings was identifi ed. This virus had been detected in six provinces and municipal cities in China as of April 18, 2013. We correlated genomic sequences from avian infl uenza viruses with ecological information and did phylogenetic and coalescent analyses to extrapolate the potential origins of the virus and possible routes of reassortment events.

Methods

We downloaded H7N9 virus genome sequences from the Global Initiative on Sharing Avian Infl uenza Data (GISAID) database and public sequences used from the Influenza Virus Resource. We constructed phylogenetic trees and did 1000 bootstrap replicates for each tree. Two rounds of phylogenetic analyses were done. We used at least 100 closely related sequences for each gene to infer the overall topology, removed suspicious sequences from the trees, and focused on the closest clades to the novel H7N9 viruses. We compared our tree topologies with those from a bayesian evolutionary analysis by sampling trees (BEAST) analysis. We used the bayesian Markov chain Monte Carlo method to jointly estimate phylogenies, divergence times, and other evolutionary parameters for all eight gene fragments. We used sequence alignment and homology-modelling methods to study specifi c mutations regarding phenotypes, specifi cally addressing the human receptor binding properties.

Findings

The novel avian infl uenza A H7N9 virus originated from multiple reassortment events. The HA gene might have originated from avian infl uenza viruses of duck origin, and the NA gene might have transferred from migratory birds infected with avian infl uenza viruses along the east Asian fl yway. The six internal genes of this virus probably originated from two diff erent groups of H9N2 avian infl uenza viruses, which were isolated from chickens. Detailed analyses also showed that ducks and chickens probably acted as the intermediate hosts leading to the emergence of this virulent H7N9 virus. Genotypic and potential phenotypic diff erences imply that the isolates causing this outbreak form two separate subclades.

Interpretation The novel avian infl uenza A H7N9 virus might have evolved from at least four origins. Diversity among isolates implies that the H7N9 virus has evolved into at least two different lineages. Unknown intermediate hosts involved might be implicated, extensive global surveillance is needed, and domestic-poultry-to-person transmission should be closely watched in the future.

Funding China Ministry of Science and Technology Project 973, National Natural Science Foundation of China, China Health and Family Planning Commission, Chinese Academy of Sciences.