X-ray structure of the hemagglutinin of a potential H3 avian progenitor of the 1968 Hong Kong pandemic influenza virus
X-ray structure of the hemagglutinin of a potential H3 avian progenitor of the 1968 Hong Kong pandemic influenza virus
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DOI：
10.1016/s0042-6822(03)00068-0
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发表时间：
2003-05-10
期刊：
影响因子：
3.7
通讯作者：
Wiley, DC
中科院分区：
文献类型：
--
作者：
Ha, Y;Stevens, DJ;Wiley, DC
我们已经确定了禽流感病毒A/duck/Ukraine/63的HA结构，该病毒与引起1968年香港流感大流行的病毒属于同一抗原亚型H3，并且可能是大流行病毒的祖病毒。我们发现鸟类和人类的ha在结构上的显著差异仅限于受体结合位点，特别是Q226L和G228S的替换，这些替换导致该位点打开，并导致其内部的残基重排，包括保守残基Y98、W153和H183。我们还分析了透明质酸与唾液五糖形成的复合物，其中末端唾液酸位于与半乳糖的α 2,3或α 2,6连锁中。比较α 2,3-链受体类似物与H3型禽血凝素或H5型禽血凝素结合的复合物结构，我们发现所有的禽流感病毒都以类似的方式与它们首选的α 2,3-链受体结合，类似物以糖苷键的反式构象结合。我们发现，alpha2,6-连锁的类似物以顺式构象与人类和禽类的ha结合，并且通过唾液酸的位置和取向的微小变化，部分解决了alpha2,6-连锁受体与alpha2,3-连锁特异性H3禽类ha结合位点的不相容性。我们讨论了我们的结果与流感病毒在物种之间转移的机制有关。(C) 2003 Elsevier Science（美国）版权所有。
We have determined the structure of the HA of an avian influenza virus, A/duck/Ukraine/63, a member of the same antigenic subtype, H3, as the virus that caused the 1968 Hong Kong influenza pandemic, and a possible progenitor of the pandemic virus. We find that structurally significant differences between the avian and the human HAs are restricted to the receptor-binding site particularly the substitutions Q226L and G228S that cause the site to open and residues within it to rearrange, including the conserved residues Y98, W153, and H183. We have also analyzed complexes formed by the HA with sialopentasaccharides in which the terminal sialic acid is in either alpha2,3-or alpha2,6-linkage to galactose. Comparing the structures of complexes in which an alpha2,3-linked receptor analog is bound to the H3 avian HA or to an H5 avian HA leads to the suggestion that all avian influenza HAs bind to their preferred alpha2,3-linked receptors similarly, with the analog in a trans conformation about the glycosidic linkage. We find that alpha2,6-linked analogs are bound by both human and avian HAs in a cis conformation, and that the incompatibility of an alpha2,6-linked receptor with the alpha2,3-linkage-specific H3 avian HA-binding site is partially resolved by a small change in the position and orientation of the sialic acid. We discuss our results in relation to the mechanism of transfer of influenza viruses between species. (C) 2003 Elsevier Science (USA). All rights reserved.