PDF(Pubmed)
Abstract：
The evolutionary pressures exerted by viral infections have led to the development of various cellular proteins with potent antiviral activities, some of which are known as antiviral restriction factors. TRIpartite Motif-containing protein 5 alpha (TRIM5α) is a well-studied restriction factor of retroviruses that exhibits virus- and host-species-specific functions in protecting against cross-primate transmission of specific lentiviruses. This specificity is achieved at the level of the host gene through positive selection predominantly within its C-terminal B30.2/PRYSPRY domain, which is responsible for the highly specific recognition of retroviral capsids. However, more recent work has challenged this paradigm, demonstrating TRIM5α as a restriction factor for retroelements as well as phylogenetically distinct viral families, acting similarly through the recognition of viral gene products via B30.2/PRYSPRY. This spectrum of antiviral activity raises questions regarding the genetic and structural plasticity of this protein as a mediator of the recognition of a potentially diverse array of viral molecular patterns. This review highlights the dynamic evolutionary footprint of the B30.2/PRYSPRY domain in response to retroviruses while exploring the guided \'specificity\' conferred by the totality of TRIM5α\'s additional domains that may account for its recently identified promiscuity.
摘要：
病毒感染所施加的进化压力导致了具有有效抗病毒活性的各种细胞蛋白的发展。其中一些被称为抗病毒限制因子。含TRIpartnal基序的蛋白5α（TRIM5α）是逆转录病毒的经过充分研究的限制因子，在保护特定慢病毒的跨灵长类动物传播方面表现出病毒和宿主物种特异性功能。这种特异性是通过主要在其C端B30.2/PRYSPRY结构域内的阳性选择在宿主基因水平上实现的，负责逆转录病毒衣壳的高度特异性识别。然而,最近的工作挑战了这种范式，证明TRIM5α是逆转录元件以及系统发育上不同病毒家族的限制因子，通过B30.2/PRYSPRY识别病毒基因产物起类似作用。该抗病毒活性谱提出了关于该蛋白质的遗传和结构可塑性作为识别潜在的多种病毒分子模式的介体的问题。这篇综述强调了B30.2/PRYSPRY域对逆转录病毒的动态进化足迹，同时探索了TRIM5α的全部其他域所赋予的指导“特异性”，这可能是其最近发现的滥交。
