Influenza A virus surface proteins are organized to help penetrate host mucus
Influenza A virus surface proteins are organized to help penetrate host mucus
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DOI：
10.7554/elife.43764
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发表时间：
2019-05-14
期刊：
影响因子：
7.7
通讯作者：
Fletcher, Daniel A.
中科院分区：
文献类型：
--
作者：
Vahey, Michael D.;Fletcher, Daniel A.
甲型流感病毒 (IAV) 通过与细胞表面的唾液酸结合进入细胞。为了实现这一目标，同时避免被宿主粘液中的唾液酸固定，病毒依赖于受体结合蛋白血凝素（HA）和受体裂解蛋白神经氨酸酶（NA）之间的平衡。尽管这种平衡的遗传方面已得到充分表征，但人们对病毒包膜中这些蛋白质的空间组织如何发挥作用知之甚少。使用位点特异性荧光标记和超分辨率显微镜，我们发现 HA 和 NA 不对称地分布在丝状病毒表面，形成结合和裂解活动的空间组织，导致病毒持续远离富含 NA 的极点。这种布朗棘轮状扩散产生持久的定向移动性，解决了病毒穿透粘液和稳定附着到底层细胞的相互冲突的需求，可能导致 IAV 临床分离株中丝状表型的流行。
Influenza A virus (IAV) enters cells by binding to sialic acid on the cell surface. To accomplish this while avoiding immobilization by sialic acid in host mucus, viruses rely on a balance between the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Although genetic aspects of this balance are well-characterized, little is known about how the spatial organization of these proteins in the viral envelope may contribute. Using site-specific fluorescent labeling and super-resolution microscopy, we show that HA and NA are asymmetrically distributed on the surface of filamentous viruses, creating a spatial organization of binding and cleaving activities that causes viruses to step consistently away from their NA-rich pole. This Brownian ratchet-like diffusion produces persistent directional mobility that resolves the virus's conflicting needs to both penetrate mucus and stably attach to the underlying cells, potentially contributing to the prevalence of the filamentous phenotype in clinical isolates of IAV.