RNF19a 通过降解 TBK1 抑制 RNA 病毒的抗病毒免疫反应。

RNF19a inhibits antiviral immune response to RNA viruses through degradation of TBK1.

机构信息

Department of Gastroenterology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China.

Emergency Department, The Aerospace Central Hospital, Beijing, 100049, China.

出版信息

Mol Immunol. 2022 Mar;143:1-6. doi: 10.1016/j.molimm.2021.12.021. Epub 2022 Jan 3.

DOI:10.1016/j.molimm.2021.12.021

PMID:34990937

Abstract

TANK-binding kinase 1 (TBK1) plays a pivotal role in antiviral innate immunity. TBK1 mediates the activation of interferon regulatory factor (IRF) 3, leading to the induction of type I IFNs (IFN-α/β) and of NF-κB signal transduction following viral infections. TBK1 must be tightly regulated to effectively control viral infections and maintain immune homeostasis. Here, we found that E3 ubiquitin ligase RNF19a mediated K48-linked ubiquitination and proteasomal degradation of TBK1. Specifically, the silence of RNF19a enhanced the production of type I interferons and suppressed RNA viral replication. Our results uncover that RNF19a acts as a negative mediator in the RIG-I signaling pathway to attenuate antiviral immune responses and suggest RNF19a as a potential therapy target in clinical infectious and inflammatory diseases.

摘要

TANK 结合激酶 1（TBK1）在抗病毒先天免疫中发挥关键作用。TBK1 介导干扰素调节因子（IRF）3 的激活，导致在病毒感染后诱导 I 型干扰素（IFN-α/β）和 NF-κB 信号转导。TBK1 必须受到严格的调控，以有效地控制病毒感染并维持免疫稳态。在这里，我们发现 E3 泛素连接酶 RNF19a 介导了 TBK1 的 K48 连接泛素化和蛋白酶体降解。具体而言，沉默 RNF19a 增强了 I 型干扰素的产生并抑制了 RNA 病毒的复制。我们的结果揭示了 RNF19a 作为 RIG-I 信号通路中的负调节剂，可减弱抗病毒免疫反应，并提示 RNF19a 可作为临床感染和炎症性疾病的潜在治疗靶点。