Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 58, Issue 8, Pages 4915-4919Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.02745-14
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Funding
- NIH [AI076119, AI100890, AI099284, AI112417, GM103368, AI079801, AI058864]
- Mizzou Advantage
- Ministry of Knowledge and Economy, Bilateral International Collaborative R&D Program, Republic of Korea
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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.
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