β-arrestin 2 as an activator of cGAS-STING signaling and target of viral immune evasion.
β-arrestin 2 as an activator of cGAS-STING signaling and target of viral immune evasion.
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β-arrestin 2 作为 cGAS-STING 信号传导的激活剂和病毒免疫逃避的目标
DOI：
10.1038/s41467-020-19849-9
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发表时间：
2020-11-26
影响因子：
16.6
通讯作者：
Yan D
中科院分区：
文献类型：
--
作者：
Zhang Y;Li M;Li L;Qian G;Wang Y;Chen Z;Liu J;Fang C;Huang F;Guo D;Zou Q;Chu Y;Yan D
Virus infection may induce excessive interferon (IFN) responses that can lead to host tissue injury or even death. β-arrestin 2 regulates multiple cellular events through the G protein-coupled receptor (GPCR) signaling pathways. Here we demonstrate that β-arrestin 2 also promotes virus-induced production of IFN-β and clearance of viruses in macrophages. β-arrestin 2 interacts with cyclic GMP-AMP synthase (cGAS) and increases the binding of dsDNA to cGAS to enhance cyclic GMP-AMP (cGAMP) production and the downstream stimulator of interferon genes (STING) and innate immune responses. Mechanistically, deacetylation of β-arrestin 2 at Lys171 facilitates the activation of the cGAS–STING signaling and the production of IFN-β. In vitro, viral infection induces the degradation of β-arrestin 2 to facilitate immune evasion, while a β-blocker, carvedilol, rescues β-arrestin 2 expression to maintain the antiviral immune response. Our results thus identify a viral immune-evasion pathway via the degradation of β-arrestin 2, and also hint that carvedilol, approved for treating heart failure, can potentially be repurposed as an antiviral drug candidate. Excessive interferon (IFN) responses often follow viral infection to induce pathology or even death. Here the authors show that a signaling adaptor, β-arrestin 2, enhances the cGAS/STING innate immunity signaling pathway to promote IFN-β production, but may be degraded in infected cells to serve as a target of viral immune evasion.
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DOI：
10.1126/science.1244040
发表时间：
2013-09-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li XD;Wu J;Gao D;Wang H;Sun L;Chen ZJ
通讯作者：
Chen ZJ
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
DOI：
10.1073/pnas.0308496101
发表时间：
2004-03-09
影响因子：
11.1
作者：
Jiang, ZF;Mak, TW;Li, XX
通讯作者：
Li, XX
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Barnett, Katherine C.;Coronas-Serna, Julia M.;Kagan, Jonathan C.
通讯作者：
Kagan, Jonathan C.