Yamashita Masahiro, Emerman Michael
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
J Virol. 2009 Oct;83(19):9835-43. doi: 10.1128/JVI.01084-09. Epub 2009 Jul 22.
The ability of human immunodeficiency virus (HIV) to infect nondividing cells is a fundamental property by which HIV replicates in critical target cells, such as macrophages and resting CD4(+) T cells. Recent studies have revealed that the capsid (CA) protein is a dominant factor that determines retrovirus infectivity in nondividing cells, and several mutations in HIV type 1 (HIV-1) CA abrogate the ability of HIV-1 to infect nondividing cells. We present evidence for a connection between cellular restriction against viral capsids and the resistance of nondividing cells to retrovirus infection. TRIM proteins that are able to target incoming viral capsids restrict HIV-1 more potently in nondividing cells than in dividing cells, thus rendering HIV-1 infection dependent on cell division. Moreover, cyclophilin A, another cellular protein that binds to HIV-1 CA, regulates HIV-1 infection of nondividing cells. Together, these data demonstrate the importance of capsid-binding cellular proteins in the control of the cell cycle independence of HIV-1. We propose that cellular restrictions to retroviral infections are themselves cell cycle dependent.
人类免疫缺陷病毒（HIV）感染非分裂细胞的能力是HIV在关键靶细胞（如巨噬细胞和静息CD4⁺ T细胞）中复制的一项基本特性。最近的研究表明，衣壳（CA）蛋白是决定逆转录病毒在非分裂细胞中感染性的主要因素，并且1型HIV（HIV-1）CA中的几个突变消除了HIV-1感染非分裂细胞的能力。我们提供了细胞对病毒衣壳的限制与非分裂细胞对逆转录病毒感染的抗性之间存在联系的证据。能够靶向进入的病毒衣壳的TRIM蛋白在非分裂细胞中比在分裂细胞中更有效地限制HIV-1，从而使HIV-1感染依赖于细胞分裂。此外，亲环素A，另一种与HIV-1 CA结合的细胞蛋白，调节HIV-1对非分裂细胞的感染。总之，这些数据证明了衣壳结合细胞蛋白在控制HIV-1细胞周期独立性方面的重要性。我们提出，细胞对逆转录病毒感染的限制本身是依赖于细胞周期的。
