Identification of calcium-modulating cyclophilin ligand as a human host restriction to HIV-1 release overcome by Vpu (Retracted article. See vol. 16, pg. 238, 2010)
Identification of calcium-modulating cyclophilin ligand as a human host restriction to HIV-1 release overcome by Vpu (Retracted article. See vol. 16, pg. 238, 2010)
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DOI：
10.1038/nm1778
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发表时间：
2008-06-01
期刊：
影响因子：
82.9
通讯作者：
Spearman, Paul
中科院分区：
文献类型：
--
作者：
Varthakavi, Vasundhara;Heimann-Nichols, Ellen;Spearman, Paul
HIV-1VPU蛋白是从人类细胞高效释放病毒所必需的。对于HIV-2，包膜蛋白(Env)取代了VPU的作用。VPU和HIV-2Env都通过抵消非洲绿猴(AGM)细胞中不存在的人类细胞内的天然宿主细胞块来促进病毒释放。在这里，我们确定钙调节亲环素配体(CAML)是一种VPU相互作用的宿主因子，限制HIV-1的释放。人CAML(由CAMLG编码)在AGM细胞中的表达对病毒的释放具有很强的抑制作用，而VPU和HIV-2Env可逆转这种抑制作用，提示CAML是这两种病毒调控因子之间的机制纽带。人类细胞中CAML的耗尽消除了VPU在促进HIV-1和小鼠白血病病毒释放方面的需要。这些结果表明，CAML是一种VPU敏感的宿主限制因子，可以抑制人类细胞释放HIV。CAML抑制病毒释放的能力应该有助于阐明新的抗HIV治疗策略。
The HIV-1 Vpu protein is required for efficient viral release from human cells. For HIV-2, the envelope (Env) protein replaces the role of Vpu. Both Vpu and HIV-2 Env enhance virus release by counteracting an innate host-cell block within human cells that is absent in African green monkey (AGM) cells. Here we identify calcium-modulating cyclophilin ligand (CAML) as a Vpu-interacting host factor that restricts HIV-1 release. Expression of human CAML (encoded by CAMLG) in AGM cells conferred a strong restriction of virus release that was reversed by Vpu and HIV-2 Env, suggesting that CAML is the mechanistic link between these two viral regulators. Depletion of CAML in human cells eliminated the need for Vpu in enhancing HIV-1 and murine leukemia virus release. These results point to CAML as a Vpu-sensitive host restriction factor that inhibits HIV release from human cells. The ability of CAML to inhibit virus release should illuminate new therapeutic strategies against HIV.