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  • Porcine Deltacoronavirus Accessory Protein NS7a Antagonizes IFN-beta Production by Competing With TRAF3 and IRF3 for Binding to IKKepsilon #MMPMID32656094
  • Fang P; Fang L; Xia S; Ren J; Zhang J; Bai D; Zhou Y; Peng G; Zhao S; Xiao S
  • Front Cell Infect Microbiol 2020[]; 10 (ä): 257 PMID32656094show ga
  • As an emerging swine enteropathogenic coronavirus, porcine deltacoronavirus (PDCoV) not only causes serious diarrhea in suckling piglets but also possesses the potential for cross-species transmission, which has sparked growing interest when studying this emerging virus. We previously identified a novel accessory protein NS7a encoded by PDCoV; however, the function of NS7a was not resolved. In this study, we demonstrated that PDCoV NS7a is an interferon antagonist. Overexpression of NS7a notably inhibited Sendai virus (SeV)-induced interferon-beta (IFN-beta) production and the activation of IRF3 rather than NF-kappaB. NS7a also inhibited IFN-beta promoter activity induced by RIG-I, MDA5, MAVS, TBK1, and IKKepsilon, which are key components of the RIG-I-like receptor (RLR) signaling pathway but not IRF3, the transcription factor downstream of TBK1/IKKepsilon. Surprisingly, NS7a specifically interacts with IKKepsilon but not with the closely related TBK1. Furthermore, NS7a interacts simultaneously with the kinase domain (KD) and the scaffold dimerization domain (SDD) of IKKepsilon, competing with TRAF3, and IRF3 for binding to IKKepsilon, leading to the reduction of RLR-mediated IFN-beta production. The interactions of TRAF3-IKKepsilon and IKKepsilon-IRF3 are also attenuated in PDCoV-infected cells. Taken together, our results demonstrate that PDCoV NS7a inhibits IFN-beta production by disrupting the association of IKKepsilon with both TRAF3 and IRF3, revealing a new mechanism utilized by a PDCoV accessory protein to evade the host antiviral innate immune response.
  • |Adaptor Proteins, Signal Transducing/metabolism[MESH]
  • |Animals[MESH]
  • |Coronavirus Infections/immunology/*metabolism/virology[MESH]
  • |Coronavirus/genetics/immunology/*metabolism[MESH]
  • |HEK293 Cells[MESH]
  • |Humans[MESH]
  • |I-kappa B Kinase/immunology/*metabolism[MESH]
  • |Immune Evasion[MESH]
  • |Interferon Regulatory Factor-3/immunology/*metabolism[MESH]
  • |Interferon-Induced Helicase, IFIH1/metabolism[MESH]
  • |Interferon-beta/*antagonists & inhibitors/biosynthesis/immunology[MESH]
  • |Receptors, Retinoic Acid/metabolism[MESH]
  • |Sendai virus/immunology/metabolism[MESH]
  • |Signal Transduction[MESH]
  • |Swine[MESH]
  • |TNF Receptor-Associated Factor 3/*metabolism[MESH]
  • |Viral Nonstructural Proteins/genetics/immunology/*metabolism[MESH]

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  • suck abstract from ncbi

    257 ä.10 2020