Department of Viral Infections, Research Institute for Microbial Disease, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Rev Med Virol. 2010 Mar;20(2):77-92. doi: 10.1002/rmv.637.
Human immunodeficiency virus type 1 (HIV-1) shows a very narrow host range limited to humans and chimpanzees. Experimentally, HIV-1 does not infect Old World monkeys, such as rhesus (Rh) and cynomolgus (CM) monkeys, and fails to replicate in activated CD4 positive T lymphocytes obtained from these monkeys. In contrast, simian immunodeficiency virus isolated from a macaque monkey (SIVmac) can replicate well in both Rh and CM. In 2004, tripartite motif 5 alpha (TRIM5 alpha) was identified as a host factor which plays an important role in the restricted host range of HIV-1. Rh and CM TRIM5 alpha restrict HIV-1 infection but not SIVmac, while in comparison, anti-viral activity of human TRIM5 alpha against those viruses is very weak. TRIM5 alpha consists of the RING, B-box 2, coiled-coil and SPRY (B30.2) domains. The RING domain is frequently found in E3 ubiquitin ligase and TRIM5 alpha is degraded via the ubiquitin-proteasome pathway during HIV-1 restriction. TRIM5 alpha recognises the multimerised capsid (viral core) of an incoming virus by its alpha-isoform specific SPRY domain and is believed to be involved in innate immunity to control retroviral infection. Differences in amino acid sequences in the SPRY domain of TRIM5 alpha of different monkey species were found to affect species-specific restriction of retrovirus infection, while differences in amino acid sequences in the viral capsid protein determine viral sensitivity to restriction. Accurate structural analysis of the binding surface between the viral capsid protein and TRIM5 alpha SPRY is thus required for the development of new antiretroviral drugs that enhance anti-HIV-1 activity of human TRIM5 alpha.
人类免疫缺陷病毒 1 型（HIV-1）表现出非常狭窄的宿主范围，仅限于人类和黑猩猩。在实验中，HIV-1不会感染旧世界猴子，如恒河猴（Rh）和食蟹猴（CM），也不能在从这些猴子中获得的激活的 CD4 阳性 T 淋巴细胞中复制。相比之下，从猕猴中分离出的猴免疫缺陷病毒（SIVmac）可以在 Rh 和 CM 中很好地复制。2004 年，三结构域蛋白 5 型（TRIM5α）被鉴定为一种宿主因子，在 HIV-1 的限制宿主范围中发挥重要作用。Rh 和 CM 的 TRIM5α 限制 HIV-1 感染，但不限制 SIVmac，而相比之下，人类 TRIM5α 对这些病毒的抗病毒活性非常弱。TRIM5α 由 RING、B-box 2、卷曲螺旋和 SPRY（B30.2）结构域组成。RING 结构域经常存在于 E3 泛素连接酶中，TRIM5α 在 HIV-1 限制过程中通过泛素-蛋白酶体途径降解。TRIM5α 通过其 alpha 同种型特异性 SPRY 结构域识别进入病毒的多聚化衣壳（病毒核心），并被认为参与控制逆转录病毒感染的先天免疫。不同猴种 TRIM5α 的 SPRY 结构域中的氨基酸序列差异影响了逆转录病毒感染的种特异性限制，而病毒衣壳蛋白中的氨基酸序列差异决定了病毒对限制的敏感性。因此，需要对病毒衣壳蛋白和 TRIM5α SPRY 之间的结合表面进行准确的结构分析，以便开发增强人类 TRIM5α 抗 HIV-1 活性的新型抗逆转录病毒药物。
