Molecular biology of rotavirus cell entry
Molecular biology of rotavirus cell entry
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DOI：
10.1016/s0188-4409(02)00374-0
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发表时间：
2002-07-01
影响因子：
7.7
通讯作者：
López, S
中科院分区：
文献类型：
--
作者：
Arias, CF;Isa, P;López, S
轮状病毒是全球婴幼儿严重脱水性腹泻的主要原因，是由三层同心蛋白质形成的无包膜病毒，这些蛋白质包围着双链RNA的基因组。轮状病毒进入上皮细胞似乎是一个多步骤的过程，在此过程中，病毒和细胞受体之间至少发生三次接触。不同的轮状病毒株对感染细胞表现出不同的要求。一些菌株依赖于细胞表面上唾液酸的存在;然而，与含唾液酸的受体的相互作用似乎不是必需的，因为不再需要唾液酸来感染细胞的变体可以从唾液酸依赖性菌株中分离出来。唾液酸依赖性轮状病毒株RRV，其神经氨酸酶抗性变体nar 3和人轮状病毒株Wa的比较表征已经允许显示，α 2 β 1整联蛋白被nar 3用作其主要细胞附着位点，并且在其与含唾液酸的细胞受体的初始接触之后的第二次相互作用中被RRV使用。前两种相互作用由病毒刺突蛋白VP 4介导。在附着到细胞上后，所有三种毒株都与整合素α V β 3和蛋白质hsc 70相互作用，这种相互作用对于病毒渗透到细胞内部可能是重要的。已发现被提议用作轮状病毒受体的细胞分子与胆固醇和鞘糖脂富集的脂质微区相关，并且这些结构域的解体极大地抑制轮状病毒的感染性。我们认为轮状病毒的功能性受体是一个复杂的几个细胞分子最有可能沉浸在质膜脂质微区。(C)2002年IMSS。出版社：Elsevier Science Inc.
Rotaviruses, the leading cause of severe dehydrating diarrhea in infants and young children worldwide, are non-enveloped viruses formed by three concentric layers of protein that enclose a genome of double-stranded RNA. The entry of rotaviruses into epithelial cells appears to be a multistep process during which at least three contacts between the virus and cell receptors occur. Different rotavirus strains display different requirements to infect cells. Some strains depend on the presence of sialic acid on the cell surface; however, interaction with a sialic acid-containing receptor does not seem to be essential, because variants that no longer need sialic acid to infect the cells can be isolated from sialic acid-dependent strains. Comparative characterization of the sialic acid-dependent rotavirus strain RRV, its neuraminidase-resistant variant nar3, and the human rotavirus strain Wa have allowed to show that alpha2beta1 integrin is used by nar3 as its primary cell attachment site, and by RRV in a second interaction subsequent to its initial contact with a sialic acid-containing cell receptor. These first two interactions are mediated by the virus spike protein VP4. After attaching to the cell, all three strains interact with integrin alphaVbeta3 and protein hsc70, interactions perhaps important for the virus to penetrate into the cell's interior. The cell molecules proposed to serve as rotavirus receptors have been found associated with cholesterol and glycosphingolipid-enriched lipid microdomains, and disorganization of these domains greatly inhibits rotavirus infectivity. We propose that the functional rotavirus receptor is a complex of several cell molecules most likely immersed in plasma membrane lipid microdomains. (C) 2002 IMSS. Published by Elsevier Science Inc.