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Severe Acute Respiratory Syndrome Coronavirus 2 ORF8 Protein Inhibits Type I Interferon Production by Targeting HSP90B1 Signaling

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that has currently infected over 430 million individuals worldwide. With the variant strains of SARS-CoV-2 emerging, a region of high mutation rates in ORF8 was identifie...

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Autores principales: Chen, Jiayi, Lu, Zixin, Yang, Xiuwen, Zhou, Yezhen, Gao, Jing, Zhang, Shihao, Huang, Shan, Cai, Jintai, Yu, Jianhai, Zhao, Wei, Zhang, Bao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168264/
https://www.ncbi.nlm.nih.gov/pubmed/35677655
http://dx.doi.org/10.3389/fcimb.2022.899546
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author Chen, Jiayi
Lu, Zixin
Yang, Xiuwen
Zhou, Yezhen
Gao, Jing
Zhang, Shihao
Huang, Shan
Cai, Jintai
Yu, Jianhai
Zhao, Wei
Zhang, Bao
author_facet Chen, Jiayi
Lu, Zixin
Yang, Xiuwen
Zhou, Yezhen
Gao, Jing
Zhang, Shihao
Huang, Shan
Cai, Jintai
Yu, Jianhai
Zhao, Wei
Zhang, Bao
author_sort Chen, Jiayi
collection PubMed
description Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that has currently infected over 430 million individuals worldwide. With the variant strains of SARS-CoV-2 emerging, a region of high mutation rates in ORF8 was identified during the early pandemic, which resulted in a mutation from leucine (L) to serine (S) at amino acid 84. A typical feature of ORF8 is the immune evasion by suppressing interferon response; however, the mechanisms by which the two variants of ORF8 antagonize the type I interferon (IFN-I) pathway have not yet been clearly investigated. Here, we reported that SARS-CoV-2 ORF8L and ORF8S with no difference inhibit the production of IFN-β, MDA5, RIG-I, ISG15, ISG56, IRF3, and other IFN-related genes induced by poly(I:C). In addition, both ORF8L and ORF8S proteins were found to suppress the nuclear translocation of IRF3. Mechanistically, the SARS-CoV-2 ORF8 protein interacts with HSP90B1, which was later investigated to induce the production of IFN-β and IRF3. Taken together, these results indicate that SARS-CoV-2 ORF8 antagonizes the RIG-I/MDA-5 signaling pathway by targeting HSP90B1, which subsequently exhibits an inhibitory effect on the production of IFN-I. These functions appeared not to be influenced by the genotypes of ORF8L and ORF8S. Our study provides an explanation for the antiviral immune suppression of SARS-CoV-2 and suggests implications for the pathogenic mechanism and treatment of COVID-19.
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spelling pubmed-91682642022-06-07 Severe Acute Respiratory Syndrome Coronavirus 2 ORF8 Protein Inhibits Type I Interferon Production by Targeting HSP90B1 Signaling Chen, Jiayi Lu, Zixin Yang, Xiuwen Zhou, Yezhen Gao, Jing Zhang, Shihao Huang, Shan Cai, Jintai Yu, Jianhai Zhao, Wei Zhang, Bao Front Cell Infect Microbiol Cellular and Infection Microbiology Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that has currently infected over 430 million individuals worldwide. With the variant strains of SARS-CoV-2 emerging, a region of high mutation rates in ORF8 was identified during the early pandemic, which resulted in a mutation from leucine (L) to serine (S) at amino acid 84. A typical feature of ORF8 is the immune evasion by suppressing interferon response; however, the mechanisms by which the two variants of ORF8 antagonize the type I interferon (IFN-I) pathway have not yet been clearly investigated. Here, we reported that SARS-CoV-2 ORF8L and ORF8S with no difference inhibit the production of IFN-β, MDA5, RIG-I, ISG15, ISG56, IRF3, and other IFN-related genes induced by poly(I:C). In addition, both ORF8L and ORF8S proteins were found to suppress the nuclear translocation of IRF3. Mechanistically, the SARS-CoV-2 ORF8 protein interacts with HSP90B1, which was later investigated to induce the production of IFN-β and IRF3. Taken together, these results indicate that SARS-CoV-2 ORF8 antagonizes the RIG-I/MDA-5 signaling pathway by targeting HSP90B1, which subsequently exhibits an inhibitory effect on the production of IFN-I. These functions appeared not to be influenced by the genotypes of ORF8L and ORF8S. Our study provides an explanation for the antiviral immune suppression of SARS-CoV-2 and suggests implications for the pathogenic mechanism and treatment of COVID-19. Frontiers Media S.A. 2022-05-23 /pmc/articles/PMC9168264/ /pubmed/35677655 http://dx.doi.org/10.3389/fcimb.2022.899546 Text en Copyright © 2022 Chen, Lu, Yang, Zhou, Gao, Zhang, Huang, Cai, Yu, Zhao and Zhang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Chen, Jiayi
Lu, Zixin
Yang, Xiuwen
Zhou, Yezhen
Gao, Jing
Zhang, Shihao
Huang, Shan
Cai, Jintai
Yu, Jianhai
Zhao, Wei
Zhang, Bao
Severe Acute Respiratory Syndrome Coronavirus 2 ORF8 Protein Inhibits Type I Interferon Production by Targeting HSP90B1 Signaling
title Severe Acute Respiratory Syndrome Coronavirus 2 ORF8 Protein Inhibits Type I Interferon Production by Targeting HSP90B1 Signaling
title_full Severe Acute Respiratory Syndrome Coronavirus 2 ORF8 Protein Inhibits Type I Interferon Production by Targeting HSP90B1 Signaling
title_fullStr Severe Acute Respiratory Syndrome Coronavirus 2 ORF8 Protein Inhibits Type I Interferon Production by Targeting HSP90B1 Signaling
title_full_unstemmed Severe Acute Respiratory Syndrome Coronavirus 2 ORF8 Protein Inhibits Type I Interferon Production by Targeting HSP90B1 Signaling
title_short Severe Acute Respiratory Syndrome Coronavirus 2 ORF8 Protein Inhibits Type I Interferon Production by Targeting HSP90B1 Signaling
title_sort severe acute respiratory syndrome coronavirus 2 orf8 protein inhibits type i interferon production by targeting hsp90b1 signaling
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168264/
https://www.ncbi.nlm.nih.gov/pubmed/35677655
http://dx.doi.org/10.3389/fcimb.2022.899546
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