Glycan topology determines human adaptation of avian H5N1 virus hemagglutinin
Glycan topology determines human adaptation of avian H5N1 virus hemagglutinin
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DOI：
10.1038/nbt1375
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发表时间：
2008-01-01
影响因子：
46.9
通讯作者：
Sasisekharan, Ram
中科院分区：
文献类型：
--
作者：
Chandrasekaran, Aarthi;Srinivasan, Aravind;Sasisekharan, Ram
甲型禽流感病毒的血凝素（HA）从禽样（α 2-3唾液化聚糖）到人样（α 2-6唾液化聚糖）受体特异性的转变被认为与它们感染人类的适应性有关（1-4）。我们发现了一种特殊的结构拓扑，而不是α 2-6链本身，能够使HA与α 2-6唾液化的聚糖特异性结合，并且这种拓扑的识别可能对HA在人类上呼吸道中与聚糖结合的适应性至关重要。综合生化、分析和数据挖掘方法表明，来自人类适应的H1N1和H3N2病毒的ha，而不是H5N1（禽流感）病毒，特异性地结合具有这种拓扑结构的长α 2-6唾液化聚糖。这可以解释为什么H5N1病毒尚未在人群中站稳脚跟（5,6）。我们的发现将有助于制定针对H5N1和可能的其他甲型流感病毒的有效监测和潜在治疗干预措施的其他战略。
A switch in specificity of avian influenza A viruses' hemagglutinin (HA) from avian-like (alpha 2-3 sialylated glycans) to human- like (alpha 2-6 sialylated glycans) receptors is believed to be associated with their adaptation to infect humans(1-4). We show that a characteristic structural topology - and not the alpha 2-6 linkage itself - enables specific binding of HA to alpha 2-6 sialylated glycans and that recognition of this topology may be critical for adaptation of HA to bind glycans in the upper respiratory tract of humans. An integrated biochemical, analytical and data mining approach demonstrates that HAs from the human- adapted H1N1 and H3N2 viruses, but not H5N1 (bird flu) viruses, specifically bind to long alpha 2-6 sialylated glycans with this topology. This could explain why H5N1 viruses have not yet gained a foothold in the human population(5,6). Our findings will enable the development of additional strategies for effective surveillance and potential therapeutic interventions for H5N1 and possibly other influenza A viruses.