Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
Virology. 2010 Apr 10;399(2):212-20. doi: 10.1016/j.virol.2010.01.003. Epub 2010 Jan 29.
The anti-retroviral restriction factor TRIM5alpha contains the RING domain, which is frequently observed in E3 ubiquitin ligases. It was previously proposed that TRIM5alpha restricts human immunodeficiency virus type 1 (HIV-1) via proteasome-dependent and -independent pathways. Here we examined the effects of RING domain mutations on retrovirus restriction by TRIM5alpha in various combinations of virus and host species. Simian immunodeficiency virus isolated from macaque (SIVmac) successfully avoided attacks by RING mutants of African green monkey (AGM)-TRIM5alpha that could still restrict HIV-1. Addition of proteasome inhibitor did not affect the anti-HIV-1 activity of AGM-TRIM5alpha, whereas it disrupted at least partly its anti-SIVmac activity. In the case of mutant human TRIM5alpha carrying proline at the position 332, however, both HIV-1 and SIVmac restrictions were eliminated as a result of RING domain mutations. These results suggested that the mechanisms of retrovirus restriction by TRIM5alpha vary depending on the combination of host and virus.
抗病毒限制因子 TRIM5alpha 含有 RING 结构域，该结构域在 E3 泛素连接酶中经常观察到。此前有人提出，TRIM5alpha 通过蛋白酶体依赖和非依赖途径限制人类免疫缺陷病毒 1 型（HIV-1）。在这里，我们研究了 RING 结构域突变对不同病毒和宿主物种中 TRIM5alpha 对逆转录病毒的限制作用。从猕猴中分离出的猴免疫缺陷病毒（SIVmac）成功地逃避了能够限制 HIV-1 的非洲绿猴（AGM）-TRIM5alpha 的 RING 突变体的攻击。添加蛋白酶体抑制剂不会影响 AGM-TRIM5alpha 的抗 HIV-1 活性，但它至少部分破坏了其抗 SIVmac 的活性。然而，对于携带 332 位脯氨酸的突变人 TRIM5alpha，RING 结构域突变导致 HIV-1 和 SIVmac 的限制均被消除。这些结果表明，TRIM5alpha 对逆转录病毒的限制机制因宿主和病毒的组合而异。
