以HIV-1为代表的慢病毒感染具有严格的种属特异性，不同宿主中存在的天然免疫限制因子可有效抵抗异源病毒感染。TRIM5α是存在于多种动物细胞中的具有识别异源慢病毒和激活天然免疫信号功能的抗病毒因子。TRIM5α泛素化被认为是其抗病毒作用的关键，我们前期研究首次证实恒河猴（Rh）TRIM5α的泛素化类型为非典型泛素化（线性泛素化和Lys27泛素化），并且这两种非典型泛素化首次在抗病毒蛋白中发现，但其具体泛素化及去泛素化酶组成及其在抗病毒作用中的具体机制不清楚。本项目拟深入研究RhTRIM5α泛素化机制，鉴定参与此非典型泛素化过程的关键去泛素化酶及泛素组装酶并评价其活性，揭示RhTRIM5α非典型泛素化对其抗病毒功能的影响及其机制。本研究预期可拓展对非典型泛素化在宿主蛋白抗病毒中的理论认知，解释慢病毒种间限制的具体分子机制。

There is strict species-specific infection of retroviruses such as HIV-1. Restriction factors are intrinsic cellular defense proteins that have evolved to block microbial infections. TRIM5a proteins recognize the viral capsids to prevent infection by both accelerating core dissociation and activating innate immunity. TRIM5a ubiquitination is considered to be the key step to the antiviral activity. We have confirmed the ubiquitination type of rhesus monkeys (Rh) TRIM5a is atypical ubiquitination (linear ubiquitination and Lys27-linked ubiquitination) for the first time. Importantly, these atypical ubiquitination is found in the antiviral protein. However the ubiquitination enzyme composition and its specific mechanism is not clear. To further reveal the influence of RhTRIM5 atypical ubiquitination on its antiviral function and its mechanism, this project intends to study the RhTRIM5 ubiquitination mechanism, identify the key deubiquitination enzymes and ubiquitination enzymes involved in this process of atypical ubiquitination, and evaluate their activities. This study is expected to expand the theoretical understanding of the role of atypical ubiquitination in the antiviral activity of host proteins and to explain the specific molecular mechanisms of interspecific restriction of lentiviruses.