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首页> 外文期刊>International Journal of Molecular Sciences >SARS Coronavirus Papain-Like Protease Inhibits the TLR7 Signaling Pathway through Removing Lys63-Linked Polyubiquitination of TRAF3 and TRAF6
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SARS Coronavirus Papain-Like Protease Inhibits the TLR7 Signaling Pathway through Removing Lys63-Linked Polyubiquitination of TRAF3 and TRAF6

机译：SARS冠状病毒类似木瓜蛋白酶的蛋白酶通过去除与TRAF3和TRAF6的Lys63连接的多聚泛素化抑制TLR7信号通路

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Severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLPro) reportedly inhibits the production of type I interferons (IFNs) and pro-inflammatory cytokines in Toll-like receptor 3 (TLR3) and retinoic acid-inducible gene 1 (RIG-I) pathways. The study investigated the inhibitory effect and its antagonistic mechanism of SARS-CoV PLPro on TLR7-mediated cytokine production. TLR7 agonist (imiquimod (IMQ)) concentration-dependently induced activation of ISRE-, NF-κB- and AP-1-luciferase reporters, as well as the production of IFN-α, IFN-β, TNF-α, IL-6 and IL-8 in human promonocyte cells. However, SARS-CoV PLPro significantly inhibited IMQ-induced cytokine production through suppressing the activation of transcription factors IRF-3, NF-κB and AP-1. Western blot analysis with anti-Lys48 and anti-Lys63 ubiquitin antibodies indicated the SARS-CoV PLPro removed Lys63-linked ubiquitin chains of TRAF3 and TRAF6, but not Lys48-linked ubiquitin chains in un-treated and treated cells. The decrease in the activated state of TRAF3 and TRAF6 correlated with the inactivation of TBK1 in response to IMQ by PLPro. The results revealed that the antagonism of SARS-CoV PLPro on TLR7-mediated innate immunity was associated with the negative regulation of TRAF3/6-TBK1-IRF3/NF-κB/AP1 signals.
机译：据报道，严重急性呼吸系统综合症冠状病毒（SARS-CoV）的木瓜蛋白酶样蛋白酶（PLPro）抑制Toll样受体3（TLR3）和视黄酸诱导基因1（I）中的I型干扰素（IFN）和促炎性细胞因子的产生。 RIG-I）途径。该研究探讨了SARS-CoV PLPro对TLR7介导的细胞因子产生的抑制作用及其拮抗机制。 TLR7激动剂（咪喹莫特（IMQ））浓度依赖性地诱导ISRE-，NF-κB-和AP-1-荧光素酶报告基因的激活以及IFN-α，IFN-β，TNF-α，IL-6的产生和人类原核细胞中的IL-8。然而，SARS-CoV PLPro通过抑制转录因子IRF-3，NF-κB和AP-1的激活，显着抑制IMQ诱导的细胞因子产生。用抗Lys48和抗Lys63泛素抗体进行的蛋白质印迹分析表明，SARS-CoV PLPro去除了未经处理和处理过的细胞中TRAF3和TRAF6的Lys63连接的泛素链，但未去除Lys48连接的泛素链。 TRAF3和TRAF6激活状态的降低与PLPro响应IMQ导致TBK1失活有关。结果表明，SARS-CoV PLPro对TLR7介导的先天免疫的拮抗作用与TRAF3 / 6-TBK1-IRF3 /NF-κB/ AP1信号的负调节有关。

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