Structures of receptor complexes of a North American H7N2 influenza hemagglutinin with a loop deletion in the receptor binding site.
Structures of receptor complexes of a North American H7N2 influenza hemagglutinin with a loop deletion in the receptor binding site.
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DOI：
10.1371/journal.ppat.1001081
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发表时间：
2010-09-02
期刊：
影响因子：
6.7
通讯作者：
Stevens J
中科院分区：
文献类型：
--
作者：
Yang H;Chen LM;Carney PJ;Donis RO;Stevens J
人类感染H7亚型禽流感病毒早在1979年就有报告。1996年，在北美H7流感病毒血凝素中出现了遗传稳定的24个核苷酸缺失，导致受体结合位点中的8个氨基酸缺失。这些病毒在活禽市场上的持续流通，以及其有记录的感染人类的能力，提出了这些病毒如何实现结构稳定性和功能性的问题。在这里，我们报告了一个详细的北美谱系亚型H7 N2病毒A/纽约/107/2003（NY 107）的受体结合位点的分子分析，包括与禽类受体类似物（3′-唾液酸-N-乙酰乳糖胺，3′SLN）和两个人受体类似物（6′-唾液酸-N-乙酰乳糖胺，6′SLN;唾液酸-N-四糖B，LST B）的复合物。结构结果表明，残基Arg 220和Arg 229（H3编号）用于补偿220环的缺失，并与受体类似物形成相互作用的一种新的机制。聚糖微阵列结果显示，NY 107保持禽类型（α2-3）受体结合特征，仅与人型（α2-6）受体中度结合。因此，尽管其受体结合位点发生了显著改变，但这种HA仍保持了功能性，并证实需要对禽类和其他动物宿主进行持续的流感病毒监测，以确定其人畜共患潜力。流感病毒对不同宿主的适应通常导致病毒表面外壳蛋白血凝素的受体特异性的转换。事实上，来自20世纪世纪最后两次人类流感大流行（1957年的H2和1968年的H3）的血凝素亚型都通过受体结合口袋中的仅两个氨基酸突变（谷氨酸226 →亮氨酸和甘氨酸228 →丝氨酸）成功地适应了人类型受体特异性。最近报告的人类感染其他禽类亚型（如H5、H7和H9）引起了公共卫生问题，并集中精力确定可能出现未来大流行毒株的潜在亚型。自1996年以来，北美血统的H7病毒一直在区域活禽市场流通，在HA的受体结合位点中含有8个氨基酸的缺失。在这里，我们报告了一个详细的结构分析的受体结合位点的血凝素从北美血统的H7 N2病毒，在复杂的禽流感和人类受体类似物，了解这些病毒如何适应这样一个戏剧性的结构变化的结合位点，而仍然是一个主要的循环病毒株。
Human infections with subtype H7 avian influenza viruses have been reported as early as 1979. In 1996, a genetically stable 24-nucleotide deletion emerged in North American H7 influenza virus hemagglutinins, resulting in an eight amino acid deletion in the receptor-binding site. The continuous circulation of these viruses in live bird markets, as well as its documented ability to infect humans, raises the question of how these viruses achieve structural stability and functionality. Here we report a detailed molecular analysis of the receptor binding site of the North American lineage subtype H7N2 virus A/New York/107/2003 (NY107), including complexes with an avian receptor analog (3′-sialyl-N-acetyllactosamine, 3′SLN) and two human receptor analogs (6′-sialyl-N-acetyllactosamine, 6′SLN; sialyllacto-N-tetraose b, LSTb). Structural results suggest a novel mechanism by which residues Arg220 and Arg229 (H3 numbering) are used to compensate for the deletion of the 220-loop and form interactions with the receptor analogs. Glycan microarray results reveal that NY107 maintains an avian-type (α2-3) receptor binding profile, with only moderate binding to human-type (α2-6) receptor. Thus despite its dramatically altered receptor binding site, this HA maintains functionality and confirms a need for continued influenza virus surveillance of avian and other animal reservoirs to define their zoonotic potential. Influenza virus adaptation to different hosts usually results in a switch in receptor specificity of the viral surface coat protein, hemagglutinin. Indeed, the hemagglutinin subtypes from the last two human influenza pandemics of the 20th Century (H2 in 1957 and H3 1968) both adapted successfully to human-type receptor specificity through only two amino acid mutations in the receptor binding pocket (Glutamine226→Leucine and Glycine228→Serine). The recent human infections reported with other avian subtypes such as H5, H7 and H9 have raised public health concerns and focused efforts on identifying potential subtypes from which a future pandemic strain may emerge. Since 1996, H7 viruses of the North American lineage have been circulating in regional live bird markets, containing an eight amino acid deletion in the receptor-binding site of HA. Here we report a detailed structural analysis of the receptor binding site of a hemagglutinin from the North American lineage of H7N2 viruses, in complex with avian and human receptor analogs, to understand how these viruses have adapted to such a dramatic structural change in the binding site while remaining one of the predominant circulating viral strains.
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影响因子：
5.4
作者：
Belser, Jessica A.;Lu, Xuihua;Tumpey, Terrence M.
通讯作者：
Tumpey, Terrence M.
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
11.8
作者：
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通讯作者：
Paetzel M
影响因子：
1.8
作者：
CHAYEN, NE;STEWART, PDS;BLOW, DM
通讯作者：
BLOW, DM
影响因子：
4.3
作者：
Guo, Chao-Tan;Takahashi, Noriko;Suzuki, Yasuo
通讯作者：
Suzuki, Yasuo