Tzarum Netanel, de Vries Robert P, Peng Wenjie, Thompson Andrew J, Bouwman Kim M, McBride Ryan, Yu Wenli, Zhu Xueyong, Verheije Monique H, Paulson James C, Wilson Ian A
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Department of Molecular Medicine and Department of Immunology and Microbiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, the Netherlands.
Cell Rep. 2017 Apr 11;19(2):235-245. doi: 10.1016/j.celrep.2017.03.054.
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 hemagglutinin (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 receptor analogs, receptor-binding studies, and tissue staining experiments illustrate the important role of the 150-loop in H10 receptor specificity.
甲型流感病毒适应新宿主是罕见事件，但却是人类中出现新的流感大流行的基础。因此，了解此类事件所涉及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H10N8病毒的病例，但H10血凝素（HA）仍保持禽类受体特异性。然而，H10 HA的150环以及相关的H7和H15亚型包含一个双残基插入，该插入可能会阻断人类受体结合。在人类大流行H2和H3病毒的受体结合位点出现的Q226L和G228S突变背景下，150环发生突变，导致获得了人类型受体特异性。带有人类和禽类受体类似物的H10 HA突变体的晶体结构、受体结合研究以及组织染色实验说明了150环在H10受体特异性中的重要作用。
