Elsevier

Virus Research

Volume 286, September 2020, 198074
Virus Research

Short communication
The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon signaling pathway

https://doi.org/10.1016/j.virusres.2020.198074Get rights and content

Highlights

  • ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 strongly inhibited type I interferon (IFN-β) activation and NF-κB pathway.

  • ORF6 and ORF8, but not nucleocapsid proteins, were capable of inhibiting ISRE-driven transcription activated by IFN-β.

  • ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibited interferon-stimulated genes (ISGs) such as ISG54 and ISG56.

  • ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 played critical roles in innate immune suppression during viral infection.

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.

Section snippets

Short communication

The pandemic of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (2019-nCoV or SARS-CoV-2) infection has become a Public Health Emergency of International Concern (PHEIC) with more than 6 million cases and 376,320 deaths as of June 2, 2020 (WHO, 2020, https://covid19.who.int). SARS-CoV-2 infection causes disorder of natural and adaptive immunity, leading to tissue damage and systemic inflammation, which is the main reason for death of COVID-19 patients (Huang et al., 2020

CRediT authorship contribution statement

Jin-Yan Li: Conceptualization, Methodology, Formal analysis, Investigation, Writing - original draft, Writing - review & editing. Ce-Heng Liao: Methodology, Formal analysis, Investigation. Qiong Wang: Formal analysis, Investigation. Yong-Jun Tan: Resources. Rui Luo: Resources. Ye Qiu: Writing - review & editing, Supervision, Funding acquisition. Xing-Yi Ge: Conceptualization, Writing - review & editing, Supervision, Funding acquisition.

Declaration of Competing Interest

The authors declare that they have no conflict of interest.

Acknowledgements

This work was jointly funded by National Natural Science Foundation of China (grant number 32041001 and 81902070), the Provincial Natural Science Foundation of Hunan Province (grant number 2019JJ20004, 2019JJ50035, and 2020SK3001).

References (13)

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