Restriction of diverse retroviruses by SAMHD1.
Restriction of diverse retroviruses by SAMHD1.
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DOI：
10.1186/1742-4690-10-26
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发表时间：
2013-03-05
期刊：
影响因子：
3.3
通讯作者：
Landau NR
中科院分区：
文献类型：
--
作者：
Gramberg T;Kahle T;Bloch N;Wittmann S;Müllers E;Daddacha W;Hofmann H;Kim B;Lindemann D;Landau NR
SAMHD 1是一种限制HIV-1和SIV在骨髓细胞中复制的三磷酸水解酶。在巨噬细胞和树突状细胞中，SAMHD 1通过将脱氧核苷酸三磷酸池减少到低于支持慢病毒逆转录的水平来限制病毒复制。HIV-2和相关SIV编码辅助蛋白Vpx，以诱导病毒进入后SAMHD 1的蛋白酶体降解。虽然SAMHD 1已被证明限制HIV-1和SIV，但其限制的广度尚不清楚，并且尚未确定其他病毒是否有对抗这种限制的方法。我们表明，SAMHD 1限制了广泛的分歧逆转录病毒，包括α，β和γ类。小鼠白血病病毒在巨噬细胞中受到SAMHD 1的限制，但去除SAMHD 1并没有减轻对感染的阻断，因为对病毒核输入的额外阻断。原型泡沫病毒（PFV）和人类T细胞白血病病毒I型（HTLV-1）是唯一测试的不受SAMHD 1限制的逆转录病毒。PFV主要在进入前逆转录，因此不受靶细胞中dNTP水平的影响。HTLV-1可能具有使病毒对SAMHD 1介导的限制性酶切产生抗性的机制。结果表明，SAMHD 1具有广泛的抗逆转录病毒活性，大多数病毒都没有发现逃避。
SAMHD1 is a triphosphohydrolase that restricts the replication of HIV-1 and SIV in myeloid cells. In macrophages and dendritic cells, SAMHD1 restricts virus replication by diminishing the deoxynucleotide triphosphate pool to a level below that which supports lentiviral reverse transcription. HIV-2 and related SIVs encode the accessory protein Vpx to induce the proteasomal degradation of SAMHD1 following virus entry. While SAMHD1 has been shown to restrict HIV-1 and SIV, the breadth of its restriction is not known and whether other viruses have a means to counteract the restriction has not been determined. We show that SAMHD1 restricts a wide array of divergent retroviruses, including the alpha, beta and gamma classes. Murine leukemia virus was restricted by SAMHD1 in macrophages yet removal of SAMHD1 did not alleviate the block to infection because of an additional block to viral nuclear import. Prototype foamy virus (PFV) and Human T cell leukemia virus type I (HTLV-1) were the only retroviruses tested that were not restricted by SAMHD1. PFV reverse transcribes predominantly prior to entry and thus is unaffected by the dNTP level in the target cell. It is possible that HTLV-1 has a mechanism to render the virus resistant to SAMHD1-mediated restriction. The results suggest that SAMHD1 has broad anti-retroviral activity against which most viruses have not found an escape.
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