The 150-Loop Restricts the Host Specificity of Human H10N8 Influenza Virus.
The 150-Loop Restricts the Host Specificity of Human H10N8 Influenza Virus.
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DOI：
10.1016/j.celrep.2017.03.054
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发表时间：
2017-04-11
期刊：
影响因子：
8.8
通讯作者：
Wilson IA
中科院分区：
文献类型：
--
作者：
Tzarum N;de Vries RP;Peng W;Thompson AJ;Bouwman KM;McBride R;Yu W;Zhu X;Verheije MH;Paulson JC;Wilson IA
甲型流感病毒对新宿主的适应是罕见的事件，但却是在人群中出现新流感大流行的基础。因此，了解这些事件的过程对于预测潜在的大流行威胁至关重要。2013年，报告了首例人感染禽H10 N8病毒的病例，但H10 HA保持了禽受体特异性。然而，H10 HA的150-环以及相关的H7和H15亚型含有两个残基插入物，其可以潜在地阻断人受体结合。在人类大流行性H2和H3病毒的受体结合位点中出现的Q226 L和G228 S突变的背景下的150环突变导致获得人型受体特异性。H10 HA突变体与人和禽类受体类似物的晶体结构、受体结合研究和组织染色实验说明了150-环在H10受体特异性中的重要作用。
Adaptation of influenza A viruses to new hosts are rare events, but are the basis for emergence of new influenza pandemics in the human population. Thus, understanding the processes involved in such events is critical for anticipating potential pandemic threats. In 2013, the first case of human infection by an avian H10N8 virus was reported, yet the H10 HA maintains avian receptor specificity. However, the 150-loop of H10 HA, as well as related H7 and H15 subtypes, contains a two-residue insert that can potentially block human receptor binding. Mutation of the 150-loop on the background of Q226L and G228S mutations, which arose in the receptor-binding site of human pandemic H2 and H3 viruses, resulted in acquisition of human-type receptor specificity. Crystal structures of H10 HA mutants with human and avian receptors analogs, receptor binding studies, and tissue staining experiments illustrate the important role of the 150-loop in H10 receptor specificity.