The Lancet: 2013 年的新型甲型 H7N9 禽流感病毒
系统发育和溯祖分析揭示了该病毒的多样性和潜在起源背景
2013 年 3 月 30 日，人们鉴定出了一种可感染人类的新型甲型 H7N9 禽流感病毒。 截至 2013 年 4 月 18 日，该病毒已在中国的六个省和多个城市中检出。 我们将禽流感病毒的基因组序列与生态学信息相关联，并进行了系统发育和溯祖分析来推断该病毒的潜在起源和可能发生基因重组事件的途径。
方法
我们从全球共享禽流感数据倡议 (GISAID) 数据库下载了 H7N9 病毒的基因组序列，并从流感病毒网络数据库 (Influenza Virus Resource) 下载了所使用的公共序列。 我们构建了系统发育树，并对每棵树进行了 1000 次自展分析重复。 我们进行了两轮系统发育分析。 我们对每个基因至少使用了 100 种相近序列来推断整体拓扑结构，从树上去除可疑序列，并侧重于与新型 H7N9 病毒最接近的演化分枝。 我们使用进化分析软件 BEAST 进行了贝叶斯进化分析，并将该分析得到的树与我们的树进行了拓扑结构比较。 我们使用贝叶斯马尔科夫链蒙特卡洛模拟法联合估计了所有八个基因片段的系统发育、分化时间以及其他演化参数。 我们使用了序列比对和同源建模方法研究了与表型有关的特定突变，特别针对性研究了人类受体的结合特性。
结果
新型甲型 H7N9 禽流感病毒起源于多个基因重组事件。 HA 基因可能起源于鸭源禽流感病毒，而 NA 基因有可能是从某些候鸟（沿东亚迁徙路线迁飞，并感染了禽流感病毒）中转移而来。 该病毒的六个内部基因可能来源于两组不同的 H9N2 禽流感病毒，这两组病毒均从鸡身上分离得到。 详细的分析还表明，鸭和鸡可能作为中间寄主而导致了此次强毒性 H7N9 病毒的出现。 基因型和潜在的表型差异意味着造成这种禽流感爆发的隔离群形成了两个独立的演化亚枝。
结果解读
新型甲型 H7N9 禽流感病毒可能至少有四个来源。 隔离群之间的多样性意味着 H7N9 病毒已经演化为至少两个不同的谱系。 其中可能涉及到未知的中间寄主，所以未来需要进行广泛的全球监测，并应密切关注国内的禽传人传播。
Liu D, Shi W, Shi Y, et al. Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses. The Lancet. 2013; doi:10.1016/S0140-6736(13)60938-1.
SummaryBackground On March 30, 2013, a novel avian infl uenza 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 Infl uenza 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 diff erent 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. “应密切关注国内的禽传人传播”。一刻也不能放松警惕。 目前还是禽传人，如果发展到人传人，后果就严重了！ 要是人传人，就成非典时期，恐惧！时刻紧记：科学防控！ 密切关注，科学防控，做好细节是院感人应做好的事！
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