Species-Specific Deamidation of RIG-I Reveals Collaborative Action between Viral and Cellular Deamidases in HSV-1 Lytic Replication.
Species-Specific Deamidation of RIG-I Reveals Collaborative Action between Viral and Cellular Deamidases in HSV-1 Lytic Replication.
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DOI：
10.1128/mbio.00115-21
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发表时间：
2021-03-30
期刊：
影响因子：
6.4
通讯作者：
Feng P
中科院分区：
文献类型：
--
作者：
Huang H;Zhao J;Wang TY;Zhang S;Zhou Y;Rao Y;Qin C;Liu Y;Chen Y;Xia Z;Feng P
疱疹病毒是人类中普遍存在的病原体，尽管宿主免疫，但其仍建立终身持久性。逃避宿主免疫应答的能力是病毒持续存在和发病的关键。视黄酸诱导基因I（Retinoicacid-induciblegene I，RIG-I）是识别来源于微生物的胞质双链RNA，诱导宿主免疫应答的传感器。病毒，如疱疹病毒，部署不同的机制来破坏RIG-I依赖的先天免疫防御。在这项研究中，我们发现，小鼠RIG-I是固有的抗脱酰胺和逃避单纯疱疹病毒1（HSV-1）。涉及人和小鼠RIG-I的比较研究表明，人RIG-I的N495决定了HSV-1 UL 37的物种特异性脱酰胺作用。值得注意的是，另一个位点N549的脱酰胺作用取决于N495的脱酰胺作用，并且它由细胞磷酸核糖焦磷酸酰胺转移酶（PPAT）催化。具体地，N495的脱酰胺化使得RIG-I能够与PPAT相互作用，导致N549的后续脱酰胺化。HSV-1需要UL 37和PPAT之间的协作来逃避RIG-I介导的抗病毒免疫应答。这项工作确定了PPAT在先天宿主防御中的免疫调节作用，并建立了由不同脱酰胺酶催化的免疫逃避的顺序脱酰胺事件。
Herpesviruses are ubiquitous pathogens in human and establish lifelong persistence despite host immunity. The ability to evade host immune response is pivotal for viral persistence and pathogenesis. Retinoic acid-inducible gene I (RIG-I) is a sensor that recognizes cytosolic double-stranded RNA derived from microbes to induce host immune response. Viruses, such as herpesviruses, deploy diverse mechanisms to derail RIG-I-dependent innate immune defense. In this study, we discovered that mouse RIG-I is intrinsically resistant to deamidation and evasion by herpes simplex virus 1 (HSV-1). Comparative studies involving human and mouse RIG-I indicate that N495 of human RIG-I dictates species-specific deamidation by HSV-1 UL37. Remarkably, deamidation of the other site, N549, hinges on that of N495, and it is catalyzed by cellular phosphoribosylpyrophosphate amidotransferase (PPAT). Specifically, deamidation of N495 enables RIG-I to interact with PPAT, leading to subsequent deamidation of N549. Collaboration between UL37 and PPAT is required for HSV-1 to evade RIG-I-mediated antiviral immune response. This work identifies an immune regulatory role of PPAT in innate host defense and establishes a sequential deamidation event catalyzed by distinct deamidases in immune evasion.
影响因子：
6.7
作者：
Feng H;Dong X;Negaard A;Feng P
通讯作者：
Feng P