Shen Lei, Wang Yini, Lin Chia-I, Liu Hung-wen, Guo Athena, Zhu X-Y
Department of Chemistry, Columbia University , New York, New York 10027, United States.
ACS Chem Biol. 2014 Aug 15;9(8):1877-84. doi: 10.1021/cb5004114. Epub 2014 Jun 27.
The binding of lectins to glycan receptors on the host cell surface is a key step contributing to the virulence and species specificity of most viruses. This is exemplified by the viral protein hemagglutinin (HA) of the influenza A virus, whose binding specificity is modulated by the linkage pattern of terminal sialic acids on glycan receptors of host epithelial cells. Such specificity dictates whether transmission is confined to a particular animal species or jumps between species. Here, we show, using H5N1 avian influenza as a model, that the specific binding of recombinant HA to α2-3 linked sialic acids can be enhanced dramatically by interaction with the surface of the lipid membrane. This effect can be quantitatively accounted for by a two-stage process in which weak association of HA with the membrane surface precedes more specific and tighter binding to the glycan receptor. The weak protein-membrane interaction discovered here in the model system may play an important secondary role in the infection and pathogenesis of the influenza A virus.
凝集素与宿主细胞表面聚糖受体的结合是决定大多数病毒毒力和物种特异性的关键步骤。甲型流感病毒的病毒蛋白血凝素（HA）就是一个例子，其结合特异性受宿主上皮细胞聚糖受体上末端唾液酸连接方式的调节。这种特异性决定了病毒传播是局限于特定动物物种还是在不同物种间跳跃。在此，我们以H5N1禽流感为模型表明，重组HA与α2-3连接的唾液酸的特异性结合可通过与脂质膜表面的相互作用而显著增强。这种效应可以通过一个两阶段过程进行定量解释，即HA先与膜表面发生弱结合，然后再与聚糖受体发生更特异、更紧密的结合。在该模型系统中发现的这种微弱的蛋白质-膜相互作用可能在甲型流感病毒的感染和发病机制中起重要的辅助作用。
