Thomas James A, Gorelick Robert J
AIDS Vaccine Program, Basic Sciences Program, SAIC-Frederick, Inc., NCI-Frederick, P.O. Box B, Building 535, Room 410, Frederick, MD 21702-1201, USA.
Virus Res. 2008 Jun;134(1-2):39-63. doi: 10.1016/j.virusres.2007.12.006. Epub 2008 Feb 14.
The role of nucleocapsid protein (NC) in the early steps of retroviral replication appears largely that of a facilitator for reverse transcription and integration. Using a wide variety of cell-free assay systems, the properties of mature NC proteins (e.g. HIV-1 p7(NC) or MLV p10(NC)) as nucleic acid chaperones have been extensively investigated. The effect of NC on tRNA annealing, reverse transcription initiation, minus-strand-transfer, processivity of reverse transcription, plus-strand-transfer, strand-displacement synthesis, 3' processing of viral DNA by integrase, and integrase-mediated strand-transfer has been determined by a large number of laboratories. Interestingly, these reactions can all be accomplished to varying degrees in the absence of NC; some are facilitated by both viral and non-viral proteins and peptides that may or may not be involved in vivo. What is one to conclude from the observation that NC is not strictly required for these necessary reactions to occur? NC likely enhances the efficiency of each of these steps, thereby vastly improving the productivity of infection. In other words, one of the major roles of NC is to enhance the effectiveness of early infection, thereby increasing the probability of productive replication and ultimately of retrovirus survival.
核衣壳蛋白(NC)在逆转录病毒复制早期步骤中的作用,很大程度上似乎是作为逆转录和整合的促进因子。利用各种各样的无细胞检测系统,已对成熟NC蛋白(如HIV-1 p7(NC)或MLV p10(NC))作为核酸伴侣的特性进行了广泛研究。许多实验室已确定了NC对tRNA退火、逆转录起始、负链转移、逆转录持续性、正链转移、链置换合成、整合酶对病毒DNA的3'加工以及整合酶介导的链转移的影响。有趣的是,在没有NC的情况下,这些反应都能在不同程度上完成;有些反应由可能参与或不参与体内过程的病毒和非病毒蛋白质及肽促进。从这些必要反应发生并不严格需要NC这一观察结果中能得出什么结论呢?NC可能会提高这些步骤中每一步的效率,从而极大地提高感染的生产率。换句话说,NC的主要作用之一是提高早期感染的有效性,从而增加有效复制的可能性以及最终逆转录病毒存活的概率。