SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates.
SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates.
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DOI：
10.1038/ni.2236
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发表时间：
2012-02-12
影响因子：
30.5
通讯作者：
中科院分区：
文献类型：
--
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SAMHD1在复制周期的早期阶段限制人类免疫缺陷病毒-1(HIV-1)感染树突状细胞和其他髓系细胞。SIVsm/HIV-2谱系病毒通过编码VPX来抵消SAMHD1介导的限制，VPX是一种病毒粒子包装的辅助蛋白，针对SAMHD1进行降解。我们证明SAMHD1通过水解细胞内的脱氧核苷酸三磷酸(DNTP)，将它们的水平降低到合成病毒基因组DNA所需的水平以下，从而限制单核细胞来源的巨噬细胞(MDM)感染HIV-1。VPX可阻断SAMHD1介导的dNTP下降。外源性脱氧核苷的加入部分缓解了MDM的这种限制。逆转录酶V148I突变降低了对dNTP的亲和力的HIV-1对SAMHD1介导的限制特别敏感。核苷酸饥饿可以作为一种机制，保护细胞免受通过DNA中间体复制的各种感染源的感染。
SAMHD1 restricts human immunodeficiency virus-1 (HIV-1) infection of dendritic and other myeloid cells at an early stage in the replication cycle. SIVsm/HIV-2 lineage viruses counteract SAMHD1-mediated restriction by encoding Vpx, a virion-packaged accessory protein that targets SAMHD1 for degradation. We show that SAMHD1 restricts HIV-1 infection of monocyte-derived macrophages (MDM) by hydrolyzing the cellular deoxynucleotide triphosphates (dNTP), reducing their level to below that required for the synthesis of the viral genomic DNA. Vpx prevented the SAMHD1-mediated decrease in dNTP. The restriction was partially alleviated in MDM by the addition of exogenous deoxynucleosides. HIV-1 with a V148I mutation in reverse transcriptase that lowers its affinity for dNTP was particularly sensitive to SAMHD1-mediated restriction. Nucleotide starvation could serve as a mechanism to protect cells from infection by a wide variety of infectious agents that replicate through a DNA intermediate.
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