School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, PR China; Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA.
Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA.
Trends Microbiol. 2019 Mar;27(3):254-267. doi: 10.1016/j.tim.2018.09.009. Epub 2018 Oct 15.
SAMHD1 is a host triphosphohydrolase that degrades intracellular deoxynucleoside triphosphates (dNTPs) to a lower level that restricts viral DNA synthesis, and thus prevents replication of diverse viruses in nondividing cells. Recent progress indicates that SAMHD1 negatively regulates antiviral innate immune responses and inflammation through interacting with various key proteins in immune signaling and DNA damage-repair pathways. SAMHD1 can also modulate antibody production in adaptive immune responses. In this review, we summarize how SAMHD1 regulates antiviral immune responses through distinct mechanisms, and discuss the implications of these new functions of SAMHD1. Furthermore, we propose important new questions and future directions that can advance functional and mechanistic studies of SAMHD1-mediated immune regulation during viral infections.
SAMHD1 是一种宿主三磷酸水解酶,可将细胞内的脱氧核苷三磷酸 (dNTP) 降解为较低水平,从而限制非分裂细胞中病毒 DNA 的合成,进而阻止多种病毒的复制。最近的研究进展表明,SAMHD1 通过与免疫信号和 DNA 损伤修复途径中的各种关键蛋白相互作用,负调控抗病毒固有免疫反应和炎症。SAMHD1 还可以调节适应性免疫反应中的抗体产生。在这篇综述中,我们总结了 SAMHD1 通过不同机制调节抗病毒免疫反应的方式,并讨论了 SAMHD1 这些新功能的意义。此外,我们还提出了一些重要的新问题和未来方向,这些问题和方向将推动病毒感染期间 SAMHD1 介导的免疫调节的功能和机制研究。