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SARS-CoV-2 NSP5 and N protein counteract the RIG-I signaling pathway by suppressing the formation of stress granules

As a highly pathogenic human coronavirus, SARS-CoV-2 has to counteract an intricate network of antiviral host responses to establish infection and spread. The nucleic acid-induced stress response is an essential component of antiviral defense and is closely related to antiviral innate immunity. Howe...

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Autores principales: Zheng, Yi, Deng, Jian, Han, Lulu, Zhuang, Meng-Wei, Xu, Yanwen, Zhang, Jing, Nan, Mei-Ling, Xiao, Yang, Zhan, Peng, Liu, Xinyong, Gao, Chengjiang, Wang, Pei-Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785035/
https://www.ncbi.nlm.nih.gov/pubmed/35075101
http://dx.doi.org/10.1038/s41392-022-00878-3
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author Zheng, Yi
Deng, Jian
Han, Lulu
Zhuang, Meng-Wei
Xu, Yanwen
Zhang, Jing
Nan, Mei-Ling
Xiao, Yang
Zhan, Peng
Liu, Xinyong
Gao, Chengjiang
Wang, Pei-Hui
author_facet Zheng, Yi
Deng, Jian
Han, Lulu
Zhuang, Meng-Wei
Xu, Yanwen
Zhang, Jing
Nan, Mei-Ling
Xiao, Yang
Zhan, Peng
Liu, Xinyong
Gao, Chengjiang
Wang, Pei-Hui
author_sort Zheng, Yi
collection PubMed
description As a highly pathogenic human coronavirus, SARS-CoV-2 has to counteract an intricate network of antiviral host responses to establish infection and spread. The nucleic acid-induced stress response is an essential component of antiviral defense and is closely related to antiviral innate immunity. However, whether SARS-CoV-2 regulates the stress response pathway to achieve immune evasion remains elusive. In this study, SARS-CoV-2 NSP5 and N protein were found to attenuate antiviral stress granule (avSG) formation. Moreover, NSP5 and N suppressed IFN expression induced by infection of Sendai virus or transfection of a synthetic mimic of dsRNA, poly (I:C), inhibiting TBK1 and IRF3 phosphorylation, and restraining the nuclear translocalization of IRF3. Furthermore, HEK293T cells with ectopic expression of NSP5 or N protein were less resistant to vesicular stomatitis virus infection. Mechanistically, NSP5 suppressed avSG formation and disrupted RIG-I–MAVS complex to attenuate the RIG-I–mediated antiviral immunity. In contrast to the multiple targets of NSP5, the N protein specifically targeted cofactors upstream of RIG-I. The N protein interacted with G3BP1 to prevent avSG formation and to keep the cofactors G3BP1 and PACT from activating RIG-I. Additionally, the N protein also affected the recognition of dsRNA by RIG-I. This study revealed the intimate correlation between SARS-CoV-2, the stress response, and innate antiviral immunity, shedding light on the pathogenic mechanism of COVID-19.
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spelling pubmed-87850352022-01-24 SARS-CoV-2 NSP5 and N protein counteract the RIG-I signaling pathway by suppressing the formation of stress granules Zheng, Yi Deng, Jian Han, Lulu Zhuang, Meng-Wei Xu, Yanwen Zhang, Jing Nan, Mei-Ling Xiao, Yang Zhan, Peng Liu, Xinyong Gao, Chengjiang Wang, Pei-Hui Signal Transduct Target Ther Article As a highly pathogenic human coronavirus, SARS-CoV-2 has to counteract an intricate network of antiviral host responses to establish infection and spread. The nucleic acid-induced stress response is an essential component of antiviral defense and is closely related to antiviral innate immunity. However, whether SARS-CoV-2 regulates the stress response pathway to achieve immune evasion remains elusive. In this study, SARS-CoV-2 NSP5 and N protein were found to attenuate antiviral stress granule (avSG) formation. Moreover, NSP5 and N suppressed IFN expression induced by infection of Sendai virus or transfection of a synthetic mimic of dsRNA, poly (I:C), inhibiting TBK1 and IRF3 phosphorylation, and restraining the nuclear translocalization of IRF3. Furthermore, HEK293T cells with ectopic expression of NSP5 or N protein were less resistant to vesicular stomatitis virus infection. Mechanistically, NSP5 suppressed avSG formation and disrupted RIG-I–MAVS complex to attenuate the RIG-I–mediated antiviral immunity. In contrast to the multiple targets of NSP5, the N protein specifically targeted cofactors upstream of RIG-I. The N protein interacted with G3BP1 to prevent avSG formation and to keep the cofactors G3BP1 and PACT from activating RIG-I. Additionally, the N protein also affected the recognition of dsRNA by RIG-I. This study revealed the intimate correlation between SARS-CoV-2, the stress response, and innate antiviral immunity, shedding light on the pathogenic mechanism of COVID-19. Nature Publishing Group UK 2022-01-24 /pmc/articles/PMC8785035/ /pubmed/35075101 http://dx.doi.org/10.1038/s41392-022-00878-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zheng, Yi
Deng, Jian
Han, Lulu
Zhuang, Meng-Wei
Xu, Yanwen
Zhang, Jing
Nan, Mei-Ling
Xiao, Yang
Zhan, Peng
Liu, Xinyong
Gao, Chengjiang
Wang, Pei-Hui
SARS-CoV-2 NSP5 and N protein counteract the RIG-I signaling pathway by suppressing the formation of stress granules
title SARS-CoV-2 NSP5 and N protein counteract the RIG-I signaling pathway by suppressing the formation of stress granules
title_full SARS-CoV-2 NSP5 and N protein counteract the RIG-I signaling pathway by suppressing the formation of stress granules
title_fullStr SARS-CoV-2 NSP5 and N protein counteract the RIG-I signaling pathway by suppressing the formation of stress granules
title_full_unstemmed SARS-CoV-2 NSP5 and N protein counteract the RIG-I signaling pathway by suppressing the formation of stress granules
title_short SARS-CoV-2 NSP5 and N protein counteract the RIG-I signaling pathway by suppressing the formation of stress granules
title_sort sars-cov-2 nsp5 and n protein counteract the rig-i signaling pathway by suppressing the formation of stress granules
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785035/
https://www.ncbi.nlm.nih.gov/pubmed/35075101
http://dx.doi.org/10.1038/s41392-022-00878-3
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