南方科技大学知识苑(SUSTech KC): The SARS-CoV-2 papain-like protease suppresses type I interferon responses by deubiquitinating STING

题名	The SARS-CoV-2 papain-like protease suppresses type I interferon responses by deubiquitinating STING
作者	Cao，Dan 1; Duan，Lian 2; Huang，Bin 1; Xiong，Yuxian 1; Zhang，Guoliang 2; Huang，Hao 1,3
通讯作者	Zhang，Guoliang; Huang，Hao
发表日期	2023
DOI	10.1126/scisignal.add0082
发表期刊	Science Signaling 影响因子和分区
ISSN	1945-0877
EISSN	1937-9145
卷号	16 期号:783
摘要	The SARS-CoV-2 papain-like protease (PLpro), which has deubiquitinating activity, suppresses the type I interferon (IFN-I) antiviral response. We investigated the mechanism by which PLpro antagonizes cellular antiviral responses. In HEK392T cells, PLpro removed K63-linked polyubiquitin chains from Lys of the stimulator of interferon genes (STING). PLpro-mediated deubiquitination of STING disrupted the STING-IKKε-IRF3 complex that induces the production of IFN-β and IFN-stimulated cytokines and chemokines. In human airway cells infected with SARS-CoV-2, the combined treatment with the STING agonist diABZi and the PLpro inhibitor GRL0617 resulted in the synergistic inhibition of SARS-CoV-2 replication and increased IFN-I responses. The PLpros of seven human coronaviruses (SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-229E, HCoV-HKU1, HCoVOC43, and HCoV-NL63) and four SARS-CoV-2 variants of concern (α, β, γ, and δ) all bound to STING and suppressed STING-stimulated IFN-I responses in HEK293T cells. These findings reveal how SARS-CoV-2 PLpro inhibits IFN-I signaling through STING deubiquitination and a general mechanism used by seven human coronaviral PLpros to dysregulate STING and to facilitate viral innate immune evasion. We also identified simultaneous pharmacological STING activation and PLpro inhibition as a potentially effective strategy for antiviral therapy against SARS-CoV-2.
相关链接	[Scopus记录]
收录类别	SCI
语种	英语
学校署名	通讯
资助项目	National Natural Science Foundation of China[21977009];National Natural Science Foundation of China[32100567];National Natural Science Foundation of China[81770012];
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Cell Biology
WOS记录号	WOS:000988282400003
出版者	AMER ASSOC ADVANCEMENT SCIENCE
Scopus记录号	2-s2.0-85158062787
来源库	Scopus
引用统计	被引频次[WOS]：21
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/536809
专题	南方科技大学第二附属医院
作者单位	1.State Key Laboratory of Chemical Oncogenomics,Guangdong Provincial Key Laboratory of Chemical Genomics,Laboratory of Structural Biology and Drug Discovery,Laboratory of Ubiquitination and Targeted Therapy,School of Chemical Biology and Biotechnology,Peking University Shenzhen Graduate School,Shenzhen,518055,China 2.National Clinical Research Center for Infectious Diseases,Shenzhen Third People’s Hospital,Southern University of Science and Technology,Shenzhen,518112,China 3.Institute of Chemical Biology,Shenzhen Bay Laboratory,Shenzhen,Guangdong,518132,China
通讯作者单位	南方科技大学第二附属医院
推荐引用方式 GB/T 7714	Cao，Dan,Duan，Lian,Huang，Bin,et al. The SARS-CoV-2 papain-like protease suppresses type I interferon responses by deubiquitinating STING[J]. Science Signaling,2023,16(783).
APA	Cao，Dan,Duan，Lian,Huang，Bin,Xiong，Yuxian,Zhang，Guoliang,&Huang，Hao.(2023).The SARS-CoV-2 papain-like protease suppresses type I interferon responses by deubiquitinating STING.Science Signaling,16(783).
MLA	Cao，Dan,et al."The SARS-CoV-2 papain-like protease suppresses type I interferon responses by deubiquitinating STING".Science Signaling 16.783(2023).