Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Universidad Andres Bello, Viña del Mar, Chile.
Cell Microbiol. 2017 Sep;19(9). doi: 10.1111/cmi.12759. Epub 2017 Jul 12.
Retroviruses are obligate intracellular parasites of eukaryotic cells. After reverse transcription, the viral DNA contained in the preintegration complex is delivered to the nucleus of the host cell, where it integrates. Before reaching the nucleus, the incoming particle and the preintegration complex must travel throughout the cytoplasm. Likewise, the newly synthesized viral proteins and viral particles must transit the cytoplasm during exit. The cytoplasm is a crowded environment, and simple diffusion is difficult. Therefore, viruses have evolved to utilize the cellular mechanisms of movement through the cytoplasm, where microtubules are the roads, and the ATP-dependent motors dynein and kinesin are the vehicles for retrograde and anterograde trafficking. This review will focus on how different retroviruses (Mazon-Pfizer monkey virus, prototype foamy virus, bovine immunodeficiency virus, human immunodeficiency virus type 1, and murine leukemia virus) have subjugated the microtubule-associated motor proteins for viral replication. Although there have been advances in our understanding of how retroviruses move along microtubules, the strategies are different among them. Thus, a better understanding of the mechanisms used by each retrovirus to functionally subvert microtubule motor proteins will provide important clues in the design of new antiretroviral drugs that can specifically disrupt intracellular viral trafficking.
逆转录病毒是真核细胞的专性细胞内寄生虫。在逆转录之后,整合前复合物中包含的病毒 DNA 被递送到宿主细胞的核内,在那里它被整合。在到达核内之前,进入的颗粒和整合前复合物必须在细胞质中穿行。同样,新合成的病毒蛋白和病毒颗粒在离开时必须穿过细胞质。细胞质是一个拥挤的环境,简单的扩散是困难的。因此,病毒已经进化到利用细胞的细胞质运动机制,其中微管是道路,而依赖于 ATP 的动力蛋白 dynein 和 kinesin 是逆行和顺行运输的车辆。这篇综述将集中讨论不同的逆转录病毒(Mazon-Pfizer 猴病毒、原型泡沫病毒、牛免疫缺陷病毒、人类免疫缺陷病毒 1 型和鼠白血病病毒)如何征服与微管相关的马达蛋白以进行病毒复制。尽管我们对逆转录病毒如何沿着微管运动有了更多的了解,但它们之间的策略是不同的。因此,更好地了解每种逆转录病毒用于功能上颠覆微管马达蛋白的机制将为设计新的抗逆转录病毒药物提供重要线索,这些药物可以特异性地破坏细胞内病毒运输。