Article ; Online: SAMHD1 has differential impact on the efficacies of HIV nucleoside reverse transcriptase inhibitors.
Antimicrobial agents and chemotherapy
2014 Volume 58, Issue 8, Page(s) 4915–4919
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) ... ...
| 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. |
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| MeSH term(s) | Adenine/analogs & derivatives ; Adenine/pharmacology ; Cell Line ; Dideoxynucleotides/metabolism ; Gene Expression ; Genes, Reporter ; HIV Reverse Transcriptase/antagonists & inhibitors ; HIV Reverse Transcriptase/genetics ; HIV Reverse Transcriptase/metabolism ; HIV-1/drug effects ; HIV-1/enzymology ; Host-Pathogen Interactions ; Humans ; Lamivudine/pharmacology ; Luciferases/genetics ; Luciferases/metabolism ; Monocytes/drug effects ; Monocytes/metabolism ; Monocytes/virology ; Monomeric GTP-Binding Proteins/antagonists & inhibitors ; Monomeric GTP-Binding Proteins/genetics ; Monomeric GTP-Binding Proteins/metabolism ; Organophosphonates/pharmacology ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Reverse Transcriptase Inhibitors/pharmacology ; SAM Domain and HD Domain-Containing Protein 1 ; Stavudine/pharmacology ; Tenofovir ; Virus Replication/drug effects ; Zidovudine/pharmacology | ||||||||||
| Chemical Substances | Dideoxynucleotides ; Organophosphonates ; RNA, Small Interfering ; Reverse Transcriptase Inhibitors ; Lamivudine (2T8Q726O95) ; Zidovudine (4B9XT59T7S) ; Tenofovir (99YXE507IL) ; Stavudine (BO9LE4QFZF) ; Luciferases (EC 1.13.12.-) ; HIV Reverse Transcriptase (EC 2.7.7.49) ; SAM Domain and HD Domain-Containing Protein 1 (EC 3.1.5.-) ; SAMHD1 protein, human (EC 3.1.5.-) ; Monomeric GTP-Binding Proteins (EC 3.6.5.2) ; Adenine (JAC85A2161) | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2014-05-27 | ||||||||||
| Publishing country | United States | ||||||||||
| Document type | Journal Article ; Research Support, N.I.H., Extramural | ||||||||||
| ZDB-ID | 217602-6 | ||||||||||
| ISSN | 1098-6596 ; 0066-4804 | ||||||||||
| ISSN (online) | 1098-6596 | ||||||||||
| ISSN | 0066-4804 | ||||||||||
| DOI | 10.1128/AAC.02745-14 | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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