SARS-CoV-2 Nucleocapsid Protein Interacts with RIG-I and Represses RIG-Mediated IFN-β Production

• Published in: Viruses Vol. 13; no. 1; p. 47
• Main Authors: Chen, Keli, Xiao, Feng, Hu, Dingwen, Ge, Weiwei, Tian, Mingfu, Wang, Wenbiao, Pan, Pan, Wu, Kailang, Wu, Jianguo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 30.12.2020; MDPI AG
• Subjects: A549 Cells; Animals; coronavirus disease 2019; COVID-19; COVID-19 - immunology; DEAD Box Protein 58 - genetics; DEAD Box Protein 58 - metabolism; HEK293 Cells; HeLa Cells; Host-Pathogen Interactions - immunology; Humans; interferon; Interferon-beta - metabolism; nucleocapsid; Nucleocapsid Proteins - metabolism; Protein Interaction Domains and Motifs; Receptors, Immunologic; SARS-CoV-2; SARS-CoV-2 - metabolism; severe acute respiratory syndrome coronavirus 2; Signal Transduction; COVID-19; IFN; nucleocapsid; retinoic acid-inducible gene I; SARS-CoV-2; severe acute respiratory syndrome coronavirus 2; coronavirus disease 2019; RIG-I; interferon
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v13010047

SARS-CoV-2 is highly pathogenic in humans and poses a great threat to public health worldwide. Clinical data shows a disturbed type I interferon (IFN) response during the virus infection. In this study, we discovered that the nucleocapsid (N) protein of SARS-CoV-2 plays an important role in the inhibition of interferon beta (IFN-β) production. N protein repressed IFN-β production induced by poly(I:C) or upon Sendai virus (SeV) infection. We noted that N protein also suppressed IFN-β production, induced by several signaling molecules downstream of the retinoic acid-inducible gene I (RIG-I) pathway, which is the crucial pattern recognition receptor (PRR) responsible for identifying RNA viruses. Moreover, our data demonstrated that N protein interacted with the RIG-I protein through the DExD/H domain, which has ATPase activity and plays an important role in the binding of immunostimulatory RNAs. These results suggested that SARS-CoV-2 N protein suppresses the IFN-β response through targeting the initial step, potentially the cellular PRR-RNA-recognition step in the innate immune pathway. Therefore, we propose that the SARS-CoV-2 N protein represses IFN-β production by interfering with RIG-I.