Isolation of an active Lv1 gene from cattle indicates that tripartite motif protein-mediated innate immunity to retroviral infection is widespread among mammals
Isolation of an active Lv1 gene from cattle indicates that tripartite motif protein-mediated innate immunity to retroviral infection is widespread among mammals
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DOI：
10.1128/jvi.00516-06
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发表时间：
2006-08-01
影响因子：
5.4
通讯作者：
Towers, Greg J.
中科院分区：
文献类型：
--
作者：
Ylinen, Laura M. J.;Keckesova, Zuzana;Towers, Greg J.
Lv 1/TRIM 5 α（tripartite motif 5 alpha）最近已成为影响包括人类在内的一系列灵长类动物对逆转录病毒感染的物种特异性耐药的重要因素。旧世界猴TRIM 5 α阻断人类免疫缺陷病毒1型（HIV-1）的感染性，人类和新世界猴TRIM 5 α蛋白对HIV-1无活性，但分别对不同的鼠（N-嗜性海洋白血病病毒[MLV-N]）和猴（来自恒河猴的猴免疫缺陷病毒[SIVmac]）逆转录病毒有活性。在这里，我们证明了第一个非灵长类动物TRIM蛋白的抗病毒活性，从牛，积极对抗不同的逆转录病毒，包括HIV-1。密切相关的人类TRIM序列的数量使得牛序列作为TRIM 5 α直系同源物的分配不确定，因此我们将其称为牛Lv 1。牛Lv 1在N-末端RING和B-box 2结构域中与灵长类TRIN 15 α蛋白密切相关，但在C-末端B30.2结构域中同源性显著较低，特别是在显示影响抗病毒特异性的区域中。有趣的是，一些受牛Lv 1限制的病毒，包括HIV-1和MLV-N，不能通过逆转录合成病毒DNA，而受限制的HIV-2则可以合成正常数量的DNA。数据支持的结论是，TRIM蛋白介导的逆转录病毒感染的限制是一个更常见的属性比以前认识到的哺乳动物。
Lv1/TRIM5 alpha (tripartite motif 5 alpha) has recently emerged as an important factor influencing species-specific permissivity to retroviral infection in a range of primates, including humans. Old World monkey TRIM5 alpha blocks human immunodeficiency virus type 1 (HIV-1) infectivity, and the human and New World monkey TRIM5 alpha proteins are inactive against HIV-1 but active against divergent murine (N-tropic marine leukemia virus [MLV-N]) and simian (simian immunodeficiency virus from rhesus macaque [SIVmac]) retroviruses, respectively. Here we demonstrate antiviral activity of the first nonprimate TRIM protein, from cattle, active against divergent retroviruses, including HIV-1. The number of closely related human TRIM sequences makes assignment of the bovine sequence as a TRIM5 alpha ortholog uncertain, and we therefore refer to it as bovine Lv1. Bovine Lv1 is closely related to primate TRIN15 alpha proteins in the N-terminal RING and B-box 2 domains but significantly less homologous in the C-terminal B30.2 domain, particularly in the region shown to influence antiviral specificity. Intriguingly, some viruses restricted by bovine Lv1, including HIV-1 and MLV-N, are unable to synthesize viral DNA by reverse transcription, whereas restricted HIV-2 makes normal amounts of DNA. The data support the conclusion that TRIM protein-mediated restriction of retroviral infection is a more common attribute of mammals than previously appreciated.