SARS-CoV-2 ORF10 suppresses the antiviral innate immune response by degrading MAVS through mitophagy
| العنوان: | SARS-CoV-2 ORF10 suppresses the antiviral innate immune response by degrading MAVS through mitophagy |
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| المؤلفون: | Wenqing Ma, Yong Zhao, Yu-wei Gao, Xingyu Li, Wenqi Wang, Hongbin He, Yudong Zhao, Tiecheng Wang, Xiaomei Ma, Xuefeng Wang, Chunqing Xu, Xue Wang, Song Jin, Peili Hou, Hongmei Wang, Zhangping Yu, Huasong Chang |
| المصدر: | Cellular and Molecular Immunology |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Proteasome Endopeptidase Complex, Immunology, Context (language use), Biology, Virus Replication, Antiviral Agents, Article, Open Reading Frames, Viral Proteins, ORF10, Interferon, Mitophagy, Autophagy, medicine, Humans, Immunology and Allergy, Gene Silencing, Adaptor Proteins, Signal Transducing, Mitochondrial antiviral-signaling protein, Innate immunity, Gene knockdown, Innate immune system, SARS-CoV-2, Ubiquitination, COVID-19, MAVS, Immunity, Innate, Mitochondria, Cell biology, NIX, HEK293 Cells, Infectious Diseases, Interferon Type I, Signal transduction, Infection, HeLa Cells, Signal Transduction, medicine.drug |
| الوصف: | The global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused severe morbidity and mortality in humans. It is urgent to understand the function of viral genes. However, the function of open reading frame 10 (ORF10), which is uniquely expressed by SARS-CoV-2, remains unclear. In this study, we showed that overexpression of ORF10 markedly suppressed the expression of type I interferon (IFN-I) genes and IFN-stimulated genes. Then, mitochondrial antiviral signaling protein (MAVS) was identified as the target via which ORF10 suppresses the IFN-I signaling pathway, and MAVS was found to be degraded through the ORF10-induced autophagy pathway. Furthermore, overexpression of ORF10 promoted the accumulation of LC3 in mitochondria and induced mitophagy. Mechanistically, ORF10 was translocated to mitochondria by interacting with the mitophagy receptor Nip3-like protein X (NIX) and induced mitophagy through its interaction with both NIX and LC3B. Moreover, knockdown of NIX expression blocked mitophagy activation, MAVS degradation, and IFN-I signaling pathway inhibition by ORF10. Consistent with our observations, in the context of SARS-CoV-2 infection, ORF10 inhibited MAVS expression and facilitated viral replication. In brief, our results reveal a novel mechanism by which SARS-CoV-2 inhibits the innate immune response; that is, ORF10 induces mitophagy-mediated MAVS degradation by binding to NIX. |
| تدمد: | 2042-0226 1672-7681 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4b935f3e86f504ab170fad1557c644fa https://doi.org/10.1038/s41423-021-00807-4 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....4b935f3e86f504ab170fad1557c644fa |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 20420226 16727681 |
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