Journal
VIROLOGY
Volume 436, Issue 2, Pages 247-254Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2012.11.010
Keywords
Retroviruses; Reverse transcriptase; dNTP pools; Nondividing Cells; SAMHD1; Vpx
Categories
Funding
- National Institutes of Health [AI077401, AI049781]
- Cellular, Biochemical, and Molecular Sciences Training Grant [GM 068411]
- Oral Cellular and Molecular Biology Training Grant [DE007202]
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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. (C) 2012 Elsevier Inc. All rights reserved.
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