Enhanced human receptor binding by H5 haemagglutinins.

Enhanced human receptor binding by H5 haemagglutinins.
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DOI:
10.1016/j.virol.2014.03.008
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发表时间:
2014-05
期刊:
影响因子:
3.7
通讯作者:
Skehel, John J.
Skehel, John J.
中科院分区:
医学3区
文献类型:
--
作者:
Xiong, Xiaoli;Xiao, Haixia;Martin, Stephen R.;Coombs, Peter J.;Liu, Junfeng;Collins, Patrick J.;Vachieri, Sebastien G.;Walker, Philip A.;Lin, Yi Pu;McCauley, John W.;Gamblin, Steven J.;Skehel, John J.

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突变的H5N1流感病毒已经从人类身上分离出来,这种病毒增加了人类受体的亲和力。我们比较了这些突变体与野生型病毒的受体结合特性,并确定了它们的血凝素与受体类似物的复合体的结构。来自越南的突变体通过获得受体结合部位附近的碱性残基,与人类受体结合得更紧密。它们与禽类受体的结合较弱,因为它们缺乏ASN-186和Gln-226之间的特异性相互作用。相反,在埃及分离的双突变株Δ133/Ile155Thr对人类受体有更强的亲和力,同时保持了野生型对禽类受体的亲和力。尽管人类受体结合增加,但与气雾剂传播的H5N1病毒不同,没有一个突变体更喜欢人类受体。然而,对人和禽类受体具有高亲和力的突变体可能是H5N1病毒进化的中间产物,H5N1病毒可能同时感染人和家禽。H5N1流感病毒结合。用生物层析干涉法检测血凝素受体的特异性。血凝素受体复合体晶体结构测定。
Mutant H5N1 influenza viruses have been isolated from humans that have increased human receptor avidity. We have compared the receptor binding properties of these mutants with those of wild-type viruses, and determined the structures of their haemagglutinins in complex with receptor analogues. Mutants from Vietnam bind tighter to human receptor by acquiring basic residues near the receptor binding site. They bind more weakly to avian receptor because they lack specific interactions between Asn-186 and Gln-226. In contrast, a double mutant, Δ133/Ile155Thr, isolated in Egypt has greater avidity for human receptor while retaining wild-type avidity for avian receptor. Despite these increases in human receptor binding, none of the mutants prefers human receptor, unlike aerosol transmissible H5N1 viruses. Nevertheless, mutants with high avidity for both human and avian receptors may be intermediates in the evolution of H5N1 viruses that could infect both humans and poultry. H5N1 influenza virus binding. Haemagglutinin receptor specificity using biolayer interferometry. Haemagglutinin receptor complex crystal structure determination.
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