Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA.
Virology. 2013 Feb 20;436(2):247-54. doi: 10.1016/j.virol.2012.11.010. Epub 2012 Dec 20.
Retroviruses consume cellular deoxynucleoside triphosphates (dNTPs) to convert their RNA genomes into proviral DNA through reverse transcription. While all retroviruses replicate in dividing cells, lentiviruses uniquely replicate in nondividing cells such as macrophages. Importantly, dNTP levels in nondividing cells are extremely low, compared to dividing cells. Indeed, a recently discovered anti-HIV/SIV restriction factor, SAMHD1, which is a dNTP triphosphohydrolase, is responsible for the limited dNTP pool of nondividing cells. Lentiviral reverse transcriptases (RT) uniquely stay functional even at the low dNTP concentrations in nondividing cells. Interestingly, Vpx of HIV-2/SIVsm proteosomally degrades SAMHD1, which elevates cellular dNTP pools and accelerates lentiviral replication in nondividing cells. These Vpx-encoding lentiviruses rapidly replicate in nondividing cells by encoding both highly functional RTs and Vpx. Here, we discuss a series of mechanistic and virological studies that have contributed to conceptually linking cellular dNTP levels and the adaptation of lentiviral replication in nondividing cells.
逆转录病毒消耗细胞中的脱氧核苷三磷酸（dNTP），通过逆转录将其 RNA 基因组转化为前病毒 DNA。虽然所有逆转录病毒都在分裂细胞中复制，但慢病毒独特地在非分裂细胞（如巨噬细胞）中复制。重要的是，与分裂细胞相比，非分裂细胞中的 dNTP 水平极低。事实上，最近发现的一种抗 HIV/SIV 限制因子 SAMHD1 是一种 dNTP 三磷酸水解酶，它负责非分裂细胞中有限的 dNTP 池。慢病毒逆转录酶（RT）即使在非分裂细胞中的低 dNTP 浓度下也能保持功能。有趣的是，HIV-2/SIVsm 的 Vpx 通过蛋白酶体降解 SAMHD1，从而提高细胞内的 dNTP 池，并加速非分裂细胞中的慢病毒复制。这些编码 Vpx 的慢病毒通过编码高效的 RT 和 Vpx，在非分裂细胞中迅速复制。在这里，我们讨论了一系列的机制和病毒学研究，这些研究有助于从概念上联系细胞内 dNTP 水平和慢病毒在非分裂细胞中的适应。
