SARS-CoV nucleocapsid protein antagonizes IFN-β response by targeting initial step of IFN-β induction pathway, and its C-terminal region is critical for the antagonism.

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV) encodes a highly basic nucleocapsid (N) protein which can inhibit the synthesis of type I interferon (IFN), but the molecular mechanism of this antagonism remains to be identified. In this study, we demonstrated that the N protein of SARS-CoV could inhibit IFN-beta (IFN-β) induced by poly(I:C) or Sendai virus. However, we found that N protein could not inhibit IFN-β production induced by overexpression of downstream signaling molecules of two important IFN-β induction pathways, toll-like receptor 3 (TLR3)- and RIG-I-like receptors (RLR)-dependent pathways. These results indicate that SARS-CoV N protein targets the initial step, probably the cellular PRRs (pattern recognition receptors)-RNAs-recognition step in the innate immune pathways, to suppress IFN expression responses. In addition, co-immunoprecipitation assays revealed that N protein did not interact with RIG-I or MDA5. Further, an assay using truncated mutants revealed that the C-terminal domain of N protein was critical for its antagonism of IFN induction, and the N deletion mutant impaired for RNA-binding almost completely lost the IFN-β antagonist activity. These results contribute to our further understanding of the pathogenesis of SARS-CoV.

• Authors: Xiaolu Lu, Ji'an Pan, Jiali Tao, Deyin Guo
• Journal: Virus genes (Virus Genes) Vol. 42 Issue 1 Pg. 37-45 (Feb 2011) ISSN: 1572-994X [Electronic] United States
• PMID: 20976535 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Coronavirus Nucleocapsid Proteins
• IRF3 protein, human
• Interferon Regulatory Factor-3
• Nucleocapsid Proteins
• RNA, Viral
• TLR3 protein, human
• Toll-Like Receptor 3
• Interferon-beta
• Protein Serine-Threonine Kinases
• DEAD-box RNA Helicases
• Poly I-C

Topics

• Adaptor Proteins, Signal Transducing (immunology)
• Cell Line
• Coronavirus Nucleocapsid Proteins
• DEAD-box RNA Helicases (immunology)
• Humans
• Interferon Regulatory Factor-3 (immunology)
• Interferon-beta (immunology, metabolism)
• Nucleocapsid Proteins (immunology)
• Poly I-C (immunology)
• Promoter Regions, Genetic
• Protein Serine-Threonine Kinases (immunology)
• RNA, Viral (analysis)
• Severe acute respiratory syndrome-related coronavirus (immunology, pathogenicity)
• Sendai virus (immunology)
• Sequence Deletion
• Toll-Like Receptor 3 (immunology)