Keli Chen1, Feng Xiao1, Dingwen Hu1, Weiwei Ge1, Mingfu Tian1, Wenbiao Wang2, Pan Pan2, Kailang Wu1, Jianguo Wu1,2,3. 1. State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China. 2. Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, China. 3. Foshan Institute of Medical Microbiology, Foshan 528315, China.
Abstract
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.
SARS-CoV-2 is highly pathogeene">nic iene">nn class="Species">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.
Authors: Stephen A Chitty; Sarah Mobbs; Brian S Rifkin; Steven W Stogner; Michael S Lewis; Jaime Betancourt; Jeffrey DellaVolpe; Fadi Abouzahr; Andrew M Wilhelm; Harold M Szerlip; Amay Parikh; Robert M Gaeta; Ian Rivera; Caroline Park; Benjamin Levi; George L Anesi; Karl C Alcover; Thomas B Arnold; Jeffrey T Howard; Kumar Sharma; Kathleen P Pratt; Ian J Stewart; Kevin K Chung Journal: Crit Care Explor Date: 2022-03-25
Authors: Yan Liu; Qi-Zhang Liang; Wan Lu; Yong-Le Yang; Ruiai Chen; Yao-Wei Huang; Bin Wang Journal: Front Immunol Date: 2021-06-16 Impact factor: 7.561