Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors
Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors
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DOI：
10.1038/nature05264
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发表时间：
2006-11-16
期刊：
影响因子：
64.8
通讯作者：
Kawaoka, Yoshihiro
中科院分区：
文献类型：
--
作者：
Yamada, Shinya;Suzuki, Yasuo;Kawaoka, Yoshihiro
H5 N1甲型流感病毒已传播到亚洲、欧洲和非洲的许多国家，不仅感染了大量家禽，而且感染了越来越多的人类，通常具有致命的影响（1，2）。人类和禽流感A病毒在识别宿主细胞受体方面存在差异：前者优先识别末端为唾液酸-α 2，6-半乳糖（SA α 2，6 Gal）的受体，而后者优先识别末端为SA α 2，3 Gal的受体（参考文献3 - 6）。从SA α 2，3Gal到SA α 2，6 Gal的识别转换被认为是禽流感病毒在人类中有效复制并获得引起大流行的潜力之前必须发生的变化之一。通过鉴定受体结合血凝素（HA）分子中的突变，使禽H5 N1病毒能够识别人型宿主细胞受体，有可能预测大流行病毒的出现（从而增加对大流行病毒的准备）。在这里，我们表明，一些从人类分离的H5 N1病毒可以结合到人类和鸟类受体，而从鸡和鸭分离的病毒，只识别鸟类受体。182和192位的突变独立地将已知识别禽类受体的H5 N1病毒的HA转化为识别人类受体的HA。我们的遗传实验中使用的来自H5 N1病毒的HA的晶体结构的分析表明，HA分子中这些氨基酸的位置与对受体结合的作用是相容的。我们鉴定的氨基酸变化可能作为评估H5 N1野外分离株大流行潜力的分子标记。
H5N1 influenza A viruses have spread to numerous countries in Asia, Europe and Africa, infecting not only large numbers of poultry, but also an increasing number of humans, often with lethal effects(1,2). Human and avian influenza A viruses differ in their recognition of host cell receptors: the former preferentially recognize receptors with saccharides terminating in sialic acid-alpha 2,6-galactose ( SA alpha 2,6Gal), whereas the latter prefer those ending in SA alpha 2,3Gal ( refs 3 - 6). A conversion from SA alpha 2,3Gal to SA alpha 2,6Gal recognition is thought to be one of the changes that must occur before avian influenza viruses can replicate efficiently in humans and acquire the potential to cause a pandemic. By identifying mutations in the receptor- binding haemagglutinin ( HA) molecule that would enable avian H5N1 viruses to recognize human- type host cell receptors, it may be possible to predict ( and thus to increase preparedness for) the emergence of pandemic viruses. Here we show that some H5N1 viruses isolated from humans can bind to both human and avian receptors, in contrast to those isolated from chickens and ducks, which recognize the avian receptors exclusively. Mutations at positions 182 and 192 independently convert the HAs of H5N1 viruses known to recognize the avian receptor to ones that recognize the human receptor. Analysis of the crystal structure of the HA from an H5N1 virus used in our genetic experiments shows that the locations of these amino acids in the HA molecule are compatible with an effect on receptor binding. The amino acid changes that we identify might serve as molecular markers for assessing the pandemic potential of H5N1 field isolates.