PMID- 23260109
OWN - NLM
STAT- MEDLINE
DCOM- 20130322
LR  - 20220331
IS  - 1096-0341 (Electronic)
IS  - 0042-6822 (Print)
IS  - 0042-6822 (Linking)
VI  - 436
IP  - 2
DP  - 2013 Feb 20
TI  - Intracellular nucleotide levels and the control of retroviral infections.
PG  - 247-54
LID - S0042-6822(12)00570-3 [pii]
LID - 10.1016/j.virol.2012.11.010 [doi]
AB  - 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.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Amie, Sarah M
AU  - Amie SM
AD  - Department of Microbiology and Immunology, University of Rochester Medical 
      Center, Rochester, NY, USA.
FAU - Noble, Erin
AU  - Noble E
FAU - Kim, Baek
AU  - Kim B
LA  - eng
GR  - GM068411/GM/NIGMS NIH HHS/United States
GR  - T32 GM068411/GM/NIGMS NIH HHS/United States
GR  - T90 DE021985/DE/NIDCR NIH HHS/United States
GR  - AI077401/AI/NIAID NIH HHS/United States
GR  - R01 AI049781/AI/NIAID NIH HHS/United States
GR  - R01 GM104198/GM/NIGMS NIH HHS/United States
GR  - R56 AI049781/AI/NIAID NIH HHS/United States
GR  - AI049781/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20121220
PL  - United States
TA  - Virology
JT  - Virology
JID - 0110674
RN  - 0 (Nucleotides)
RN  - 0 (VPX protein, Human immunodeficiency virus 2)
RN  - 0 (VPX protein, Simian immunodeficiency virus)
RN  - 0 (Viral Regulatory and Accessory Proteins)
RN  - EC 3.1.5.- (SAM Domain and HD Domain-Containing Protein 1)
RN  - EC 3.1.5.- (SAMHD1 protein, human)
RN  - EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - Cytoplasm/*chemistry
MH  - Humans
MH  - Lentivirus/*physiology
MH  - Monomeric GTP-Binding Proteins/metabolism
MH  - Nucleotides/analysis/*metabolism
MH  - Retroviridae/*physiology
MH  - *Reverse Transcription
MH  - SAM Domain and HD Domain-Containing Protein 1
MH  - Viral Regulatory and Accessory Proteins/metabolism
MH  - *Virus Replication
PMC - PMC3804251
MID - NIHMS430661
EDAT- 2012/12/25 06:00
MHDA- 2013/03/23 06:00
PMCR- 2014/02/20
CRDT- 2012/12/25 06:00
PHST- 2012/09/19 00:00 [received]
PHST- 2012/09/24 00:00 [revised]
PHST- 2012/11/17 00:00 [accepted]
PHST- 2012/12/25 06:00 [entrez]
PHST- 2012/12/25 06:00 [pubmed]
PHST- 2013/03/23 06:00 [medline]
PHST- 2014/02/20 00:00 [pmc-release]
AID - S0042-6822(12)00570-3 [pii]
AID - 10.1016/j.virol.2012.11.010 [doi]
PST - ppublish
SO  - Virology. 2013 Feb 20;436(2):247-54. doi: 10.1016/j.virol.2012.11.010. Epub 2012 
      Dec 20.