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The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon signaling pathway.
Virus Res. 2020 09; 286:198074.VR

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human coronavirus causing the pandemic of severe pneumonia (Coronavirus Disease 2019, COVID-19). SARS-CoV-2 is highly pathogenic in human, having posed immeasurable public health challenges to the world. Innate immune response is critical for the host defense against viral infection and the dysregulation of the host innate immune responses probably aggravates SARS-CoV-2 infection, contributing to the high morbidity and lethality of COVID-19. It has been reported that some coronavirus proteins play an important role in modulating innate immunity of the host, but few studies have been conducted on SARS-CoV-2. In this study, we screened the viral proteins of SARS-CoV-2 and found that the viral ORF6, ORF8 and nucleocapsid proteins were potential inhibitors of type I interferon signaling pathway, a key component for antiviral response of host innate immune. All the three proteins showed strong inhibition on type I interferon (IFN-β) and NF-κB-responsive promoter, further examination revealed that these proteins were able to inhibit the interferon-stimulated response element (ISRE) after infection with Sendai virus, while only ORF6 and ORF8 proteins were able to inhibit the ISRE after treatment with interferon beta. These findings would be helpful for the further study of the detailed signaling pathway and unveil the key molecular player that may be targeted.

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Authors+Show Affiliations

Li JY
Institute of Pathogen Biology and Immunology, College of Biology, Hunan Provincial Key Laboratory of Medical Virology, Hunan University, Changsha 410082, Hunan, China. Electronic address: lijinyan@hnu.edu.cn.
Liao CH
Institute of Pathogen Biology and Immunology, College of Biology, Hunan Provincial Key Laboratory of Medical Virology, Hunan University, Changsha 410082, Hunan, China. Electronic address: liaoceheng@hnu.edu.cn.
Wang Q
Institute of Pathogen Biology and Immunology, College of Biology, Hunan Provincial Key Laboratory of Medical Virology, Hunan University, Changsha 410082, Hunan, China. Electronic address: qw@hnu.edu.cn.
Tan YJ
Institute of Pathogen Biology and Immunology, College of Biology, Hunan Provincial Key Laboratory of Medical Virology, Hunan University, Changsha 410082, Hunan, China. Electronic address: yjtan@hnu.edu.cn.
Luo R
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, Hubei, China. Electronic address: luorui@mail.hzau.edu.cn.
Qiu Y
Institute of Pathogen Biology and Immunology, College of Biology, Hunan Provincial Key Laboratory of Medical Virology, Hunan University, Changsha 410082, Hunan, China. Electronic address: qiuye@hnu.edu.cn.
Ge XY
Institute of Pathogen Biology and Immunology, College of Biology, Hunan Provincial Key Laboratory of Medical Virology, Hunan University, Changsha 410082, Hunan, China. Electronic address: xyge@hnu.edu.cn.

MeSH

BetacoronavirusCoronavirus Nucleocapsid ProteinsGene Expression RegulationGenes, ReporterHEK293 CellsHost-Pathogen InteractionsHumansImmunity, InnateInfluenza A Virus, H1N1 SubtypeInterferon-betaLuciferasesNF-kappa BNucleocapsid ProteinsPhosphoproteinsPlasmidsRecombinant ProteinsResponse ElementsSARS-CoV-2Sendai virusSignal TransductionTransfectionViral Proteins

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32589897

Citation

Li, Jin-Yan, et al. "The ORF6, ORF8 and Nucleocapsid Proteins of SARS-CoV-2 Inhibit Type I Interferon Signaling Pathway." Virus Research, vol. 286, 2020, p. 198074.
Li JY, Liao CH, Wang Q, et al. The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon signaling pathway. Virus Res. 2020;286:198074.
Li, J. Y., Liao, C. H., Wang, Q., Tan, Y. J., Luo, R., Qiu, Y., & Ge, X. Y. (2020). The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon signaling pathway. Virus Research, 286, 198074. https://doi.org/10.1016/j.virusres.2020.198074
Li JY, et al. The ORF6, ORF8 and Nucleocapsid Proteins of SARS-CoV-2 Inhibit Type I Interferon Signaling Pathway. Virus Res. 2020;286:198074. PubMed PMID: 32589897.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon signaling pathway. AU - Li,Jin-Yan, AU - Liao,Ce-Heng, AU - Wang,Qiong, AU - Tan,Yong-Jun, AU - Luo,Rui, AU - Qiu,Ye, AU - Ge,Xing-Yi, Y1 - 2020/06/23/ PY - 2020/06/18/received PY - 2020/06/21/revised PY - 2020/06/22/accepted PY - 2020/6/27/pubmed PY - 2020/9/9/medline PY - 2020/6/27/entrez KW - Accessory proteins KW - COVID-19 KW - Interferon KW - SARS-CoV-2 KW - Structural proteins SP - 198074 EP - 198074 JF - Virus research JO - Virus Res VL - 286 N2 - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human coronavirus causing the pandemic of severe pneumonia (Coronavirus Disease 2019, COVID-19). SARS-CoV-2 is highly pathogenic in human, having posed immeasurable public health challenges to the world. Innate immune response is critical for the host defense against viral infection and the dysregulation of the host innate immune responses probably aggravates SARS-CoV-2 infection, contributing to the high morbidity and lethality of COVID-19. It has been reported that some coronavirus proteins play an important role in modulating innate immunity of the host, but few studies have been conducted on SARS-CoV-2. In this study, we screened the viral proteins of SARS-CoV-2 and found that the viral ORF6, ORF8 and nucleocapsid proteins were potential inhibitors of type I interferon signaling pathway, a key component for antiviral response of host innate immune. All the three proteins showed strong inhibition on type I interferon (IFN-β) and NF-κB-responsive promoter, further examination revealed that these proteins were able to inhibit the interferon-stimulated response element (ISRE) after infection with Sendai virus, while only ORF6 and ORF8 proteins were able to inhibit the ISRE after treatment with interferon beta. These findings would be helpful for the further study of the detailed signaling pathway and unveil the key molecular player that may be targeted. SN - 1872-7492 UR - https://www.unboundmedicine.com/medline/citation/32589897/The_ORF6_ORF8_and_nucleocapsid_proteins_of_SARS_CoV_2_inhibit_type_I_interferon_signaling_pathway_ DB - PRIME DP - Unbound Medicine ER -