Retrovirus resistance factors Ref1 and Lv1 are species-specific variants of TRIM5α
Retrovirus resistance factors Ref1 and Lv1 are species-specific variants of TRIM5α
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DOI：
10.1073/pnas.0402361101
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发表时间：
2004-07-20
影响因子：
11.1
通讯作者：
Bieniasz, PD
中科院分区：
文献类型：
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作者：
Hatziioannou, T;Perez-Caballero, D;Bieniasz, PD
哺乳动物细胞表达以细胞自主方式起作用以抑制逆转录病毒复制的几种因子。其中包括Friend病毒易感因子1/慢病毒易感因子1/限制因子1（Ref 1）类限制因子，它们通过靶向不同逆转录病毒的衣壳来阻断感染。在这里，我们表明，慢病毒易感因子1和Ref 1是物种特异性的三重相互作用基序5 α（TRIM 5 α），细胞质体组件最近被证明可以阻止HIV-1感染恒河猴细胞的变体，并确实可以阻止广泛不同的逆转录病毒感染。从人类细胞中去除TRIM 5 α可以解除N-嗜性鼠白血病病毒（N-MLV）的限制，而在其他非限制性细胞中表达人类TRIM 5 α可以赋予对N-MLV感染的特异性抗性，这表明TRIM 5 α是Ref 1或Ref 1的重要组成部分。来自人类、恒河猴和非洲绿色猴的TRIM 5 α变体显示出不同但重叠的限制特异性，这些特异性通过它们所来源的细胞的限制特性相当准确地预测。所有TRIM 5 α变体都能抑制至少两种不同逆转录病毒的感染，非洲绿色猴TRIM 5 α能够抑制不少于四种人、非人灵长类、马和鼠来源的不同逆转录病毒的感染。然而，每个TRIM 5 α变体都不能限制从相同物种分离的逆转录病毒。这些数据表明，TRIM 5 α可以赋予灵长类细胞对逆转录病毒感染的广泛先天免疫，并且可能是跨物种逆转录病毒传播的重要天然屏障。
Mammalian cells express several factors that act in a cell-autonomous manner to inhibit retrovirus replication. Among these are the Friend virus susceptibility factor 1/lentivirus susceptibility factor 1/restriction factor 1 (Ref1) class of restriction factors, which block infection by targeting the capsids of diverse retroviruses. Here we show that lentivirus susceptibility factor 1 and Ref1 are species-specific variants of tripartite interaction motif 5alpha (TRIM5alpha), a cytoplasmic body component recently shown to block HIV-1 infection in rhesus macaque cells, and can indeed block infection by widely divergent retroviruses. Depletion of TRIM5alpha from human cells relieved restriction of N-tropic murine leukemia virus (N-MLV), and expression of human TRIM5alpha in otherwise nonrestricting cells conferred specific resistance to N-MLV infection, indicating that TRIM5alpha is Ref1 or an essential component of Ref1. TRIM5alpha variants from humans, rhesus monkeys, and African green monkeys displayed different but overlapping restriction specificities that were quite accurately predicted by the restriction properties of the cells from which they were derived. All TRIM5alpha variants could inhibit infection by at least two different retroviruses, and African green monkey TRIM5alpha was able to inhibit infection by no less than four divergent retroviruses of human, non-human primate, equine, and murine origin. However, each TRIM5alpha variant was unable to restrict retroviruses isolated from the same species. These data indicate that TRIM5alpha can confer broad innate immunity to retrovirus infection in primate cells and is likely to be an important natural barrier to cross-species retrovirus transmission.