P Body-Associated Protein Mov10 Inhibits HIV-1 Replication at Multiple Stages
P Body-Associated Protein Mov10 Inhibits HIV-1 Replication at Multiple Stages
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DOI：
10.1128/jvi.00585-10
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发表时间：
2010-10-01
影响因子：
5.4
通讯作者：
Pathak, Vinay K.
中科院分区：
文献类型：
--
作者：
Burdick, Ryan;Smith, Jessica L.;Pathak, Vinay K.
最近的研究表明，APOBEC3G(A3G)是一种有效的人类免疫缺陷病毒1型(HIV-1)复制抑制剂，定位于细胞质的mRNA加工体(P体)。然而，A3G与P体标记物蛋白共定位的功能相关性尚未建立。为了探讨HIV-1、A3G和P小体之间的关系，我们分析了P小体标记蛋白Mov10、DCP1a和DCP2过表达对HIV-1复制的影响。我们的结果表明，Mov10的过表达导致了在多个阶段对HIV-1复制的有效抑制。Mov10是一种可能的RNA解旋酶，以前被报道属于DExD超家族，最近被报道属于UPF1样解旋酶，而不是解帽酶DCP1a和DCP2。Mov10在病毒产生细胞中的过表达导致HIV-1 Gag蛋白和病毒生产的稳定水平下降；Mov10有效地整合到病毒粒子中，并降低了病毒的传染性，部分是通过抑制反转录。此外，A3G和Mov10过表达减少了HIV-1 Gag的蛋白降解过程。A3G和Mov10的抑制作用是相加的，这意味着两种抑制剂之间缺乏功能相互作用。小干扰RNA(SiRNA)介导的内源性Mov10被敲除80%后，病毒产量减少了2倍，但对p24输入的病毒感染性没有明显影响，表明内源性Mov10不是病毒感染性所必需的。总体而言，这些结果表明，Mov10可以在多个阶段有效地抑制HIV-1复制。
Recent studies have shown that APOBEC3G (A3G), a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) replication, is localized to cytoplasmic mRNA-processing bodies (P bodies). However, the functional relevance of A3G colocalization with P body marker proteins has not been established. To explore the relationship between HIV-1, A3G, and P bodies, we analyzed the effects of overexpression of P body marker proteins Mov10, DCP1a, and DCP2 on HIV-1 replication. Our results show that overexpression of Mov10, a putative RNA helicase that was previously reported to belong to the DExD superfamily and was recently reported to belong to the Upf1-like group of helicases, but not the decapping enzymes DCP1a and DCP2, leads to potent inhibition of HIV-1 replication at multiple stages. Mov10 overexpression in the virus producer cells resulted in reductions in the steady-state levels of the HIV-1 Gag protein and virus production; Mov10 was efficiently incorporated into virions and reduced virus infectivity, in part by inhibiting reverse transcription. In addition, A3G and Mov10 overexpression reduced proteolytic processing of HIV-1 Gag. The inhibitory effects of A3G and Mov10 were additive, implying a lack of functional interaction between the two inhibitors. Small interfering RNA (siRNA)-mediated knockdown of endogenous Mov10 by 80% resulted in a 2-fold reduction in virus production but no discernible impact on the infectivity of the viruses after normalization for the p24 input, suggesting that endogenous Mov10 was not required for viral infectivity. Overall, these results show that Mov10 can potently inhibit HIV-1 replication at multiple stages.