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SAMHD1 host restriction factor: A link with innate immune sensing of retrovirus infection

机译:SAMHD1宿主限制因子:与逆转录病毒感染的固有免疫感知有关

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摘要

SAMHD1 [sterile alpha motif and histidine-aspartic domain (HD) containing protein 1] is the most recent addition to a unique group of host restriction factors that limit retroviral replication at distinct stages of the viral life cycle. SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase that degrades the intracellular pool of deoxynucleoside triphosphates available during early reverse transcription. SAMHD1 activity is blocked by the Vpx accessory function present in human immunodeficiency virus type 2 and SIVsm. Mutations in SAMHD1 are associated with the autoimmune disorder Aicardi-Goutières syndrome, thus emphasizing its role in regulation of the immune response. SAMHD1 antiretroviral activity is modulated by post-translational modifications, cell-cycle-dependent functions and cytokine-mediated changes. Innate receptors that sense retroviral DNA intermediates are the focus of intense study, and recent studies have established a link among SAMHD1 restriction, innate sensing of DNA and protective immune responses. Cell-cycle-dependent regulation of SAMHD1 by phosphorylation and the increasingly broad range of viruses inhibited by SAMHD1 further emphasize the importance of these mechanisms of host restriction. This review highlights current knowledge regarding SAMHD1 regulation and its impact on innate immune signaling and retroviral restriction.
机译:SAMHD1 [含有蛋白质1的无菌α序列和组氨酸-天冬氨酸结构域(HD)]是一组独特的宿主限制因子的最新成员,它们在病毒生命周期的不同阶段限制了逆转录病毒的复制。 SAMHD1是一种脱氧核苷三磷酸三磷酸水解酶,可降解早期逆转录过程中可用的脱氧核苷三磷酸的细胞内池。 SAMHD1活性被2型人类免疫缺陷病毒和SIVsm中的Vpx辅助功能所阻断。 SAMHD1中的突变与自身免疫性疾病Aicardi-Goutières综合征相关,因此强调了其在调节免疫反应中的作用。 SAMHD1抗逆转录病毒活性通过翻译后修饰,细胞周期依赖性功能和细胞因子介导的变化来调节。感应逆转录病毒DNA中间体的先天受体是深入研究的重点,最近的研究已经建立了SAMHD1限制,DNA的先天感测和保护性免疫应答之间的联系。 SAMHD1通过磷酸化的细胞周期依赖性调控以及越来越广泛的被SAMHD1抑制的病毒进一步强调了这些宿主限制性机制的重要性。这篇综述重点介绍了有关SAMHD1调控及其对先天免疫信号和逆转录病毒限制的影响的最新知识。

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