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Antimicrob Agents Chemother. 2014 Aug;58(8):4915-9. doi: 10.1128/AAC.02745-14. Epub 2014 May 27.

SAMHD1 has differential impact on the efficacies of HIV nucleoside reverse transcriptase inhibitors.

Author information

1
Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri, USA.
2
Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA Department of Molecular Microbiology & Immunology, University of Missouri School of Medicine, Columbia, Missouri, USA.
3
Microbiology Department, New York University School of Medicine, New York, New York, USA.
4
Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA Department of Molecular Microbiology & Immunology, University of Missouri School of Medicine, Columbia, Missouri, USA Department of Biochemistry, University of Missouri, Columbia, Missouri, USA sarafianoss@missouri.edu.

Abstract

Sterile alpha motif- and histidine/aspartic acid domain-containing protein 1 (SAMHD1) limits HIV-1 replication by hydrolyzing deoxynucleoside triphosphates (dNTPs) necessary for reverse transcription. Nucleoside reverse transcriptase inhibitors (NRTIs) are components of anti-HIV therapies. We report here that SAMHD1 cleaves NRTI triphosphates (TPs) at significantly lower rates than dNTPs and that SAMHD1 depletion from monocytic cells affects the susceptibility of HIV-1 infections to NRTIs in complex ways that depend not only on the relative changes in dNTP and NRTI-TP concentrations but also on the NRTI activation pathways.

PMID:
24867973
PMCID:
PMC4136039
DOI:
10.1128/AAC.02745-14
[Indexed for MEDLINE]
Free PMC Article

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