Departamento de Bioquímica y Biología Molecular I, Universidad Complutense, Madrid, Spain.
FEBS J. 2011 Sep;278(17):2997-3011. doi: 10.1111/j.1742-4658.2011.08252.x. Epub 2011 Aug 8.
After fusion with the cellular plasma membrane or endosomal membranes, viral particles are generally too large to diffuse freely within the crowded cytoplasm environment. Thus, they will never reach the cell nucleus or the perinuclear areas where replication or reverse transcription usually takes place. It has been proposed that many unrelated viruses are transported along microtubules in a retrograde manner using the cellular dynein machinery or, at least, some dynein components. A putative employment of the dynein motor in a dynein-mediated transport has been suggested from experiments in which viral capsid proteins were used as bait in yeast two-hybrid screens using libraries composed of cellular proteins and dynein-associated chains were retrieved as virus-interacting proteins. In most cases DYNLL1, DYNLT1 or DYNLRB1 were identified as the dynein chains that interact with viral proteins. The importance of these dynein-virus interactions has been supported, in principle, by the observation that in some cases the dynein-interacting motifs of viral proteins altered by site-directed mutagenesis result in non-infective virions. Furthermore, overexpression of p50 dynamitin, which blocks the dynein-dynactin interaction, or incubation of infected cells with peptides that compete with viral polypeptides for dynein binding have been shown to alter the viral retrograde transport. Still, it remains to be proved that dynein light chains can bind simultaneously to incoming virions and to the dynein motor for retrograde transport to take place. In this review, we will analyse the association of viral proteins with dynein polypeptides and its implications for viral infection.
融合到细胞质膜或内体膜后，病毒颗粒通常太大，无法在拥挤的细胞质环境中自由扩散。因此，它们永远不会到达复制或逆转录通常发生的细胞核或核周区域。有人提出，许多不相关的病毒使用细胞动力蛋白机械以逆行方式沿微管运输，或者至少使用一些动力蛋白成分。在使用病毒衣壳蛋白作为酵母双杂交筛选中诱饵的实验中，提出了在动力蛋白介导的运输中使用动力蛋白马达的假设，该实验中使用的文库由细胞蛋白和动力蛋白相关链组成，并检索到病毒相互作用蛋白。在大多数情况下，DYNLL1、DYNLT1 或 DYNLRB1 被鉴定为与病毒蛋白相互作用的动力蛋白链。这些动力蛋白-病毒相互作用的重要性原则上得到了支持，因为在某些情况下，病毒蛋白的动力蛋白相互作用基序通过定点诱变改变会导致非感染性病毒颗粒。此外，过表达 p50 动力蛋白 dynamitin，其阻断动力蛋白-dynactin 相互作用，或用与病毒多肽竞争结合动力蛋白的肽孵育感染细胞，已被证明会改变病毒逆行运输。不过，仍然需要证明动力蛋白轻链可以同时与传入的病毒颗粒和逆行运输的动力蛋白马达结合。在这篇综述中，我们将分析病毒蛋白与动力蛋白多肽的关联及其对病毒感染的影响。
