Npro of Classical Swine Fever Virus Suppresses Type III Interferon Production by Inhibiting IRF1 Expression and Its Nuclear Translocation

Viruses. 2019 Oct 31;11(11):998. doi: 10.3390/v11110998.

Abstract

Classical swine fever virus (CSFV) causes a contagious disease of pigs. The virus can break the mucosal barrier to establish its infection. Type III interferons (IFN-λs) play a crucial role in maintaining the antiviral state in epithelial cells. Limited information is available on whether or how CSFV modulates IFN-λs production. We found that IFN-λ3 showed dose-dependent suppression of CSFV replication in IPEC-J2 cells. Npro-deleted CSFV mutant (∆Npro) induced significantly higher IFN-λs transcription from 24 h post-infection (hpi) than its parental strain (wtCSFV). The strain wtCSFV strongly inhibited IFN-λs transcription and IFN-λ3 promoter activity in poly(I:C)-stimulated IPEC-J2 cells, whereas ∆Npro did not show such inhibition. Npro overexpression caused significant reduction of IFN-λs transcription and IFN-λ3 promoter activity. Both wtCSFV and ∆Npro infection induced time-dependent IRF1 expression in IPEC-J2 cells, with ΔNpro showing more significant induction, particularly at 24 hpi. However, infection with wtCSFV or Npro overexpression led not only to significant reduction of IRF1 expression and its promoter activity in poly(I:C)-treated IPEC-J2 cells but also to blockage of IRF1 nuclear translocation. This study provides clear evidence that CSFV Npro suppresses IRF1-mediated type III IFNs production by inhibiting IRF1 expression and its nuclear translocation.

Keywords: IRF1; Npro; Type III interferons; classical swine fever virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / immunology
  • Animals
  • Cell Line
  • Classical Swine Fever / immunology*
  • Classical Swine Fever / virology
  • Classical Swine Fever Virus* / genetics
  • Classical Swine Fever Virus* / metabolism
  • Endopeptidases* / genetics
  • Endopeptidases* / metabolism
  • Gene Expression Regulation
  • Host-Pathogen Interactions
  • Immunity, Innate
  • Interferon Lambda
  • Interferon Regulatory Factor-1 / metabolism
  • Interferons / metabolism*
  • Mutation / genetics
  • Swine
  • Swine Diseases / immunology
  • Swine Diseases / virology
  • Viral Proteins* / genetics
  • Viral Proteins* / metabolism

Substances

  • Interferon Regulatory Factor-1
  • Viral Proteins
  • Interferons
  • Endopeptidases
  • N(pro) protein, swine fever virus
  • Interferon Lambda