The Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Inhibits Type I Interferon Production by Interfering with TRIM25-Mediated RIG-I Ubiquitination.
Severe acute respiratory syndrome (SARS) is a respiratory disease, caused by a coronavirus (SARS-CoV), that is characterized by atypical pneumonia. The nucleocapsid protein (N protein) of SARS-CoV plays an important role in inhibition of type I interferon (IFN) production via an unknown mechanism. In this study, the SARS-CoV N protein was found to bind to the SPRY domain of the tripartite motif protein 25 (TRIM25) E3 ubiquitin ligase, thereby interfering with the association between TRIM25 and retinoic acid-inducible gene I (RIG-I) and inhibiting TRIM25-mediated RIG-I ubiquitination and activation. Type I IFN production induced by poly I·C or Sendai virus (SeV) was suppressed by the SARS-CoV N protein. SARS-CoV replication was increased by overexpression of the full-length N protein but not N amino acids 1 to 361, which could not interact with TRIM25. These findings provide an insightful interpretation of the SARS-CoV-mediated host innate immune suppression caused by the N protein.IMPORTANCEThe SARS-CoV N protein is essential for the viral life cycle and plays a key role in the virus-host interaction. We demonstrated that the interaction between the C terminus of the N protein and the SPRY domain of TRIM25 inhibited TRIM25-mediated RIG-I ubiquitination, which resulted in the inhibition of IFN production. We also found that the Middle East respiratory syndrome CoV (MERS-CoV) N protein interacted with TRIM25 and inhibited RIG-I signaling. The outcomes of these findings indicate the function of the coronavirus N protein in modulating the host's initial innate immune response.
State Key Laboratory of Pathogen Biosecurity, Beijing Institute of Biotechnology, Beijing, China.
Yong
Y
Hu
State Key Laboratory of Pathogen Biosecurity, Beijing Institute of Biotechnology, Beijing, China.
Wei
W
Li
State Key Laboratory of Pathogen Biosecurity, Beijing Institute of Biotechnology, Beijing, China.
Ting
T
Gao
State Key Laboratory of Pathogen Biosecurity, Beijing Institute of Biotechnology, Beijing, China.
Yan
Y
Cui
State Key Laboratory of Pathogen Biosecurity, Beijing Institute of Biotechnology, Beijing, China.
Yanwen
Y
Jin
State Key Laboratory of Pathogen Biosecurity, Beijing Institute of Biotechnology, Beijing, China.
Ping
P
Li
State Key Laboratory of Pathogen Biosecurity, Beijing Institute of Biotechnology, Beijing, China.
Qingjun
Q
Ma
State Key Laboratory of Pathogen Biosecurity, Beijing Institute of Biotechnology, Beijing, China liux931932@163.com cao_c@sohu.com.
Xuan
X
Liu
State Key Laboratory of Pathogen Biosecurity, Beijing Institute of Biotechnology, Beijing, China liux931932@163.com cao_c@sohu.com.
Cheng
C
Cao
D000818:Animals; D002460:Cell Line; D000086462:Coronavirus Nucleocapsid Proteins; D006801:Humans; D057131:Immune Evasion; D007108:Immune Tolerance; D007370:Interferon Type I / Q000378:metabolism*; D019590:Nucleocapsid Proteins / Q000378:metabolism*; D011485:Protein Binding; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D000070584:Tripartite Motif Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D014779:Virus Replication
D000086462:Coronavirus Nucleocapsid Proteins; D007370:Interferon Type I; D019590:Nucleocapsid Proteins; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; C522809:RNF135 protein, human; C084523:TRIM25 protein, human; D044767:Ubiquitin-Protein Ligases
RIG-I; SARS coronavirus; TRIM25; interferon; nucleocapsid