Khalfi Soumia, Mérindol Natacha, Berthoux Lionel
Département de biologie médicale, Université du Québec à Trois-Rivières, Trois-Rivières, Québec, Canada.
Virologie (Montrouge). 2020 Dec 1;24(6):369-380. doi: 10.1684/vir.2020.0869.
In this review, we summarize recent advances in the knowledge of the biological functions of human TRIM5α, a cytoplasmic protein mostly known for its antiretroviral functions. In addition to directly targeting retroviral capsid cores, an inhibitory activity called "restriction", TRIM5α senses retroviruses and activates NF-κB and AP-1 signaling pathways, resulting in the production of type I interferon (IFN-I). The antiviral state resulting from the activation of these pathways includes the upregulation of other restriction factors, and is thought to be important for the control of HIV-1 in some patients. TRIM5α also targets the protease enzyme of several tick-borne flaviviruses, a family of viruses not closely related to retroviruses. In addition to these antiviral functions, TRIM5α promotes autophagy by interacting with key actors of this pathway, such as ULK1 and p62. TRIM5α may function as a selective autophagy receptor in some conditions. Altogether, our understanding of TRIM5α shows its potential for the development of medical applications in viral diseases and beyond.
在本综述中,我们总结了关于人类TRIM5α生物学功能的最新知识进展,TRIM5α是一种主要因其抗逆转录病毒功能而为人所知的细胞质蛋白。除了直接靶向逆转录病毒衣壳核心(一种称为“限制”的抑制活性)外,TRIM5α还能感知逆转录病毒并激活NF-κB和AP-1信号通路,从而导致I型干扰素(IFN-I)的产生。这些通路激活所产生的抗病毒状态包括其他限制因子的上调,并且被认为对某些患者控制HIV-1很重要。TRIM5α还靶向几种蜱传黄病毒的蛋白酶,蜱传黄病毒是一类与逆转录病毒关系不密切的病毒。除了这些抗病毒功能外,TRIM5α还通过与该通路的关键因子(如ULK1和p62)相互作用来促进自噬。在某些情况下,TRIM5α可能作为一种选择性自噬受体发挥作用。总之,我们对TRIM5α的理解表明了其在病毒疾病及其他领域开发医学应用的潜力。