Chwetzoff S, Trugnan G
INSERM-UPMC UMR 538, "Membrane traffic and signalization in epithelial cells", CHU Saint-Antoine, 27 rue de Chaligny, 75012 Paris, France.
Curr Top Microbiol Immunol. 2006;309:245-61. doi: 10.1007/3-540-30773-7_9.
We review here recent advances in our knowledge on trafficking and assembly of rotavirus and rotaviral proteins in intestinal cells. Assembly of rotavirus has been extensively studied in nonpolarized kidney epithelial MA104 cells, where several data indicate that most if not all the steps of rotavirus assembly take place within the endoplasmic reticulum (ER) and that rotavirus is release upon cell lysis. We focus here on data obtained in intestinal cells that argue for another scheme of rotavirus assembly, where the final steps seem to take place outside the ER with an apically polarized release of rotavirus without significant cell lysis. One of the key observations made by different groups is that VP4 and other structural proteins interact substantially with specialized membrane microdomains enriched in cholesterol and sphingolipids termed rafts. In addition, recent data point to the fact that VP4 does not localize within the ER or the Golgi apparatus in infected intestinal cells. The mechanisms by which VP4, a cytosolic protein, may be targeted to the apical membrane in these cells and assembles with the other structural proteins are discussed. The identification of cellular proteins such as Hsp70, flotillin, rab5, PRA1 and cytoskeletal components that interact with VP4 may help to define an atypical polarized trafficking pathway to the apical membrane of intestinal cells that will be raft-dependent and by-pass the classical exocytic route.
我们在此综述了关于轮状病毒及其蛋白在肠道细胞中的运输和组装方面的最新研究进展。轮状病毒的组装已在非极化的肾上皮MA104细胞中得到广泛研究，多项数据表明，轮状病毒组装的大部分（如果不是全部）步骤发生在内质网（ER）内，并且轮状病毒在细胞裂解时释放。我们在此关注在肠道细胞中获得的数据，这些数据支持另一种轮状病毒组装模式，即最终步骤似乎发生在内质网之外，轮状病毒以顶端极化的方式释放，且细胞无明显裂解。不同研究团队的一项关键观察结果是，VP4和其他结构蛋白与富含胆固醇和鞘脂的特殊膜微结构域（称为脂筏）大量相互作用。此外，最近的数据表明，在受感染的肠道细胞中，VP4并不定位于内质网或高尔基体。本文讨论了胞质蛋白VP4在这些细胞中靶向顶端膜并与其他结构蛋白组装的机制。对与VP4相互作用的细胞蛋白（如Hsp70、flotillin、rab5、PRA1和细胞骨架成分）的鉴定，可能有助于确定一条非典型的极化运输途径，该途径通向肠道细胞的顶端膜，依赖脂筏且绕过经典的胞吐途径。
