Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses
Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses
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DOI：
10.1016/s0140-6736(13)60938-1
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发表时间：
2013-06-01
期刊：
影响因子：
168.9
通讯作者：
Gao, George F.
中科院分区：
文献类型：
--
作者：
Liu, Di;Shi, Weifeng;Gao, George F.
背景2013年3月30日，发现了一种感染人类的新型甲型H7N9禽流感病毒。截至2013年4月18日，该病毒已在中国六个省市被发现。我们相关的基因组序列从禽流感病毒与生态信息，并做系统发育和合并分析，以推断潜在的起源的病毒和可能的路线的重配events.Methods我们下载H7N9病毒基因组序列从全球倡议共享禽流感数据（GISAID）数据库和公共序列从流感病毒资源。我们构建了系统发育树，并为每棵树做了1000次自举重复。进行了两轮系统发育分析。我们使用每个基因至少100个密切相关的序列来推断整体拓扑结构，从树中删除可疑序列，并专注于与新型H7N9病毒最接近的分支。我们比较了我们的树的拓扑结构与那些从baidu进化分析抽样树（BEAST）分析。我们使用baidu马尔可夫链蒙特卡罗方法来联合估计所有八个基因片段的遗传、发散时间和其他进化参数。我们使用序列比对和同源性建模方法来研究特定的突变表型，特别是解决人类受体binding properties.Findings的新型禽流感A H7N9病毒起源于多个重配事件。HA基因可能来源于鸭源禽流感病毒，NA基因可能来自于禽流感病毒沿着东亚迁徙路线的候鸟。该病毒的六个内部基因可能来自两组不同的H9 N2禽流感病毒，这两组病毒是从鸡中分离的。详细的分析还表明，鸭和鸡可能是导致这种强毒H7N9病毒出现的中间宿主。基因型和潜在的表型差异意味着引起这次疫情的分离株形成两个独立的亚支。分离株之间的多样性意味着H7N9病毒已经进化成至少两个不同的谱系。可能涉及未知的中间宿主，需要进行广泛的全球监测，未来应密切关注家禽-人传播。
Background On March 30, 2013, a novel avian influenza A H7N9 virus that infects human beings was identified. This virus had been detected in six provinces and municipal cities in China as of April 18, 2013. We correlated genomic sequences from avian influenza 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 Influenza 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 specific mutations regarding phenotypes, specifically addressing the human receptor binding properties.Findings The novel avian influenza A H7N9 virus originated from multiple reassortment events. The HA gene might have originated from avian influenza viruses of duck origin, and the NA gene might have transferred from migratory birds infected with avian influenza viruses along the east Asian flyway. The six internal genes of this virus probably originated from two different groups of H9N2 avian influenza 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 differences imply that the isolates causing this outbreak form two separate subclades.Interpretation The novel avian influenza 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.