SAMHD1对HIV核苷类逆转录酶抑制剂的疗效有不同影响。
SAMHD1 has differential impact on the efficacies of HIV nucleoside reverse transcriptase inhibitors.
作者信息
Huber Andrew D, Michailidis Eleftherios, Schultz Megan L, Ong Yee T, Bloch Nicolin, Puray-Chavez Maritza N, Leslie Maxwell D, Ji Juan, Lucas Anthony D, Kirby Karen A, Landau Nathaniel R, Sarafianos Stefan G
机构信息
Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri, USA.
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.
出版信息
Antimicrob Agents Chemother. 2014 Aug;58(8):4915-9. doi: 10.1128/AAC.02745-14. Epub 2014 May 27.
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.
摘要
含无菌α基序和组氨酸/天冬氨酸结构域蛋白1（SAMHD1）通过水解逆转录所需的脱氧核苷三磷酸（dNTP）来限制HIV-1复制。核苷类逆转录酶抑制剂（NRTI）是抗HIV疗法的组成部分。我们在此报告，SAMHD1切割NRTI三磷酸酯（TP）的速率明显低于dNTP，并且单核细胞中SAMHD1的缺失以复杂的方式影响HIV-1感染对NRTI的敏感性，这些方式不仅取决于dNTP和NRTI-TP浓度的相对变化，还取决于NRTI激活途径。
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