ArticlesOrigin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses
Introduction
On March 30, 2013, a novel avian influenza A H7N9 virus causing human infections was identified in China.1 As of April 18, 2013, the virus had spread to six provinces and municipal cities—ie, Shanghai, Anhui, Jiangsu, Zhejiang, Beijing, and Henan. To our knowledge, this outbreak represents the first time that the H7N9 subtype has infected people and caused fatal cases (as of April 18, 2013, 87 people have been infected and 17 have died). In modern times, H7 subtype avian influenza viruses, including H7N1, H7N2, H7N3 and H7N7, have caused more than 100 human infections, including a fatal case in the Netherlands.2, 3, 4 In wild birds, H7 and N9 avian influenza viruses have evolved to American, Oceanian, and Eurasian lineages.5, 6 Preliminary analyses1 have shown that the H7N9 viruses causing the 2013 outbreak in China are novel reassortants, the HA gene originated from avian influenza viruses circulating in ducks in Zhejiang Province, the NA gene is related to avian influenza viruses isolated from wild birds, and the internal genes probably orinigated from an earlier H9N2 lineage. Kageyama and colleagues7 have postulated that the internal genes originated from poultry viruses. In this study, we integrated data from phylogenetic analyses, coalescent analyses, and host ecology to infer the potential origins and genetic diversity of the novel avian influenza A H7N9 viruses.
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Sequence alignment
We downloaded the H7N9 virus genome sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) database—specifically, A/Anhui/1/2013 (Anhui/1), EPI439503∼EPI439510; A/Shanghai/1/2013 (Shanghai/1), EPI439486∼EPI439491, EPI439493, EPI439494; A/Shanghai/2/2013 (Shanghai/2), EPI439495∼EPI439502; and A/Hangzhou/1/2013 (Hangzhou/1), EPI440095∼EPI440097. We downloaded all the public sequences used from the Influenza Virus Resource.8 CLC Main Workbench (CLC Bio, Aarhus, Denmark) was
Results
The phylogeny of the H7 gene sequences available showed three main independent lineages—ie, American, Oceanian, and Eurasian lineages. The novel H7N9 virus fell within the Eurasian lineage, and was genetically close to sequences isolated from ducks in Zhejiang Province in 2011 (Figure 1, Figure 2). The H7 phylogenetic tree also showed that varied H7 viruses were circulating in wild ducks along the east Asian flyway, which covers eastern China, South Korea, and Japan. Genetic exchange between
Discussion
Tracing the origin of the novel H7N9 virus is of vital importance for formulation of effective prevention and surveillance policies. We propose at least four possible gene-segment origins are proposed for the novel H7N9 virus (panel).
The estimated time to most recent common ancestor of the novel H7N9 strain was during the wintering period for wild birds. Thus, corresponding H7 strains might have been circulating in poultry (most likely in ducks) for at least 1 year.
An earlier H11N9 strain of
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