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SARS-CoV-2 ORF10 antagonizes STING-dependent interferon activation and autophagy.
Han, Lulu; Zheng, Yi; Deng, Jian; Nan, Mei-Ling; Xiao, Yang; Zhuang, Meng-Wei; Zhang, Jing; Wang, Wei; Gao, Chengjiang; Wang, Pei-Hui.
Afiliación
  • Han L; Department of Immunology, Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • Zheng Y; Department of Immunology, Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • Deng J; Key Laboratory for Experimental Teratology of Ministry of Education and Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • Nan ML; Key Laboratory for Experimental Teratology of Ministry of Education and Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • Xiao Y; Key Laboratory for Experimental Teratology of Ministry of Education and Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • Zhuang MW; Key Laboratory for Experimental Teratology of Ministry of Education and Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • Zhang J; Key Laboratory for Experimental Teratology of Ministry of Education and Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • Wang W; School of Medical Imaging, Weifang Medical University, Weifang, China.
  • Gao C; Department of Immunology, Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • Wang PH; Key Laboratory for Experimental Teratology of Ministry of Education and Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China.
J Med Virol ; 94(11): 5174-5188, 2022 11.
Article en En | MEDLINE | ID: mdl-35765167
A characteristic feature of COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is the dysregulated immune response with impaired type I and III interferon (IFN) expression and an overwhelming inflammatory cytokine storm. RIG-I-like receptors (RLRs) and cGAS-STING signaling pathways are responsible for sensing viral infection and inducing IFN production to combat invading viruses. Multiple proteins of SARS-CoV-2 have been reported to modulate the RLR signaling pathways to achieve immune evasion. Although SARS-CoV-2 infection also activates the cGAS-STING signaling by stimulating micronuclei formation during the process of syncytia, whether SARS-CoV-2 modulates the cGAS-STING pathway requires further investigation. Here, we screened 29 SARS-CoV-2-encoded viral proteins to explore the viral proteins that affect the cGAS-STING signaling pathway and found that SARS-CoV-2 open reading frame 10 (ORF10) targets STING to antagonize IFN activation. Overexpression of ORF10 inhibits cGAS-STING-induced interferon regulatory factor 3 phosphorylation, translocation, and subsequent IFN induction. Mechanistically, ORF10 interacts with STING, attenuates the STING-TBK1 association, and impairs STING oligomerization and aggregation and STING-mediated autophagy; ORF10 also prevents the endoplasmic reticulum (ER)-to-Golgi trafficking of STING by anchoring STING in the ER. Taken together, these findings suggest that SARS-CoV-2 ORF10 impairs the cGAS-STING signaling by blocking the translocation of STING and the interaction between STING and TBK1 to antagonize innate antiviral immunity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interferón Tipo I / COVID-19 Límite: Humans Idioma: En Revista: J Med Virol Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interferón Tipo I / COVID-19 Límite: Humans Idioma: En Revista: J Med Virol Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos