title: Intracellular nucleotide levels and the control of retroviral infections.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Amie
authors.forename: Erin
authors.initials: E
authors.lastname: Noble
authors.forename: Baek
authors.initials: B
authors.lastname: Kim
mesh_terms: D000818:Animals; D003593:Cytoplasm / Q000737:chemistry*; D006801:Humans; D016086:Lentivirus / Q000502:physiology*; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D009711:Nucleotides / Q000032:analysis / Q000378:metabolism*; D012190:Retroviridae / Q000502:physiology*; D048348:Reverse Transcription; D000076106:SAM Domain and HD Domain-Containing Protein 1; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism; D014779:Virus Replication
chemical_list: D009711:Nucleotides; C074286:VPX protein, Human immunodeficiency virus 2; C513059:VPX protein, Simian immunodeficiency virus; D054334:Viral Regulatory and Accessory Proteins; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins