Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein
Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein
复制标题
DOI：
10.1038/nature00939
复制
发表时间：
2002-08-08
期刊：
影响因子：
64.8
通讯作者：
Malim, MH
中科院分区：
文献类型：
--
作者：
Sheehy, AM;Gaddis, NC;Malim, MH
病毒已经发展了多种非免疫策略来对抗赋予对感染的抗性的宿主介导的机制。Vif（病毒体感染因子）蛋白由灵长类免疫缺陷病毒编码，最显著的是人类免疫缺陷病毒-1（HIV-1）。这些蛋白质是病毒感染和复制的有效调节剂，因此是体内致病性感染所必需的（1-6）。HIV-1 Vif似乎在病毒产生的晚期阶段是必需的（3，6），用于抑制存在于人T淋巴细胞中的先天性抗病毒表型（7，8）。因此，在不存在Vif的情况下，该表型的表达使得子代病毒粒子不具有感染性。在这里，我们描述了一种独特的细胞基因，CEM 15，其在通常不表达CEM 15的细胞中的瞬时或稳定表达重建了这种表型，但其抗病毒作用被Vif的存在所克服。因为Vif：CEM 15调控通路是HIV-1复制的关键通路，干扰该通路可能是未来HIV/AIDS治疗的一个有希望的靶点。
Viruses have developed diverse non-immune strategies to counteract host-mediated mechanisms that confer resistance to infection. The Vif (virion infectivity factor) proteins are encoded by primate immunodeficiency viruses, most notably human immunodeficiency virus-1 (HIV-1). These proteins are potent regulators of virus infection and replication and are consequently essential for pathogenic infections in vivo(1-6). HIV-1 Vif seems to be required during the late stages of virus production(3,6) for the suppression of an innate antiviral phenotype that resides in human T lymphocytes(7,8). Thus, in the absence of Vif, expression of this phenotype renders progeny virions non-infectious. Here, we describe a unique cellular gene, CEM15, whose transient or stable expression in cells that do not normally express CEM15 recreates this phenotype, but whose antiviral action is overcome by the presence of Vif. Because the Vif: CEM15 regulatory circuit is critical for HIV-1 replication, perturbing the circuit may be a promising target for future HIV/AIDS therapies.