title: SAMHD1 has differential impact on the efficacies of HIV nucleoside reverse transcriptase inhibitors.
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.
authors.affiliation: Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Huber
authors.affiliation: 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.
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Michailidis
authors.affiliation: Microbiology Department, New York University School of Medicine, New York, New York, USA.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Schultz
authors.affiliation: 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.
authors.forename: Yee T
authors.initials: YT
authors.lastname: Ong
authors.affiliation: Microbiology Department, New York University School of Medicine, New York, New York, USA.
authors.forename: Nicolin
authors.initials: N
authors.lastname: Bloch
authors.affiliation: 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.
authors.forename: Maritza N
authors.initials: MN
authors.lastname: Puray-Chavez
authors.affiliation: 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.
authors.forename: Maxwell D
authors.initials: MD
authors.lastname: Leslie
authors.affiliation: 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.
authors.forename: Juan
authors.initials: J
authors.lastname: Ji
authors.affiliation: 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.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Lucas
authors.affiliation: 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.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Kirby
authors.affiliation: Microbiology Department, New York University School of Medicine, New York, New York, USA.
authors.forename: Nathaniel R
authors.initials: NR
authors.lastname: Landau
authors.affiliation: 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.
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Sarafianos
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D054306:Dideoxynucleotides / Q000378:metabolism*; D015870:Gene Expression; D017930:Genes, Reporter; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D054884:Host-Pathogen Interactions; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D020559:Monomeric GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D063065:Organophosphonates / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D000076106:SAM Domain and HD Domain-Containing Protein 1; D018119:Stavudine / Q000494:pharmacology; D000068698:Tenofovir; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D054306:Dideoxynucleotides; D063065:Organophosphonates; D034741:RNA, Small Interfering; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D000068698:Tenofovir; D018119:Stavudine; D008156:Luciferases; D054303:HIV Reverse Transcriptase; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins; D000225:Adenine