An anti-interferon activity shared by paramyxovirus C proteins: inhibition of Toll-like receptor 7/9-dependent alpha interferon induction

FEBS Lett. 2014 Jan 3;588(1):28-34. doi: 10.1016/j.febslet.2013.11.015. Epub 2013 Nov 20.

Abstract

Paramyxovirus C protein targets the host interferon (IFN) system for virus immune evasion. To identify its unknown anti-IFN activity, we examined the effect of Sendai virus C protein on activation of the IFN-α promoter via various signaling pathways. This study uncovers a novel ability of C protein to block Toll-like receptor (TLR) 7- and TLR9-dependent IFN-α induction, which is specific to plasmacytoid dendritic cells. C protein interacts with a serine/threonine kinase IKKα and inhibits phosphorylation of IRF7. This anti-IFN activity of C protein is shared across genera of the Paramyxovirinae, and thus appears to play an important role in paramyxovirus immune evasion.

Keywords: C protein; ELISA; IFN; IFN-stimulated genes; IFN-β promoter stimulator-1; IKKα; IPS-1; IRAK1; IRF; ISGs; Interferon-α; IκB kinase alpha; MDA5; MeV; MyD88; N; NiV; Nipah virus; ORF; P; PAMPs; PIVs; PKR; Paramyxovirus; RIG-I; RIG-I-like receptors; RLRs; SDS; SeV; Sendai virus; TIR-domain-containing adapter-inducing interferon-β; TLR; TLR7; TRAF6; TRIF; Toll-like receptor; bPIV3; bovine PIV type 3; double stranded; ds; enzyme-linked immunosorbent assay; interferon; interferon regulatory factor; interleukin-1 receptor-associated kinase 1; mAb; measles virus; melanoma differentiation-associated gene 5; monoclonal antibody; myeloid differentiation factor 88; nucleocapsid protein; open reading frame; pAb; pDC; pDCs; parainfluenza viruses; pathogen-associated molecular patterns; phosphoprotein; plasmacytoid dendritic cells; polyclonal antibody; protein kinase R; retinoic acid-inducible gene-I; sodium dodecyl sulfate; tumor necrosis factor receptor-associated 6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chlorocebus aethiops
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology
  • HEK293 Cells
  • Host-Pathogen Interactions / immunology
  • Humans
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism
  • Immunoblotting
  • Interferon Regulatory Factor-7 / genetics
  • Interferon Regulatory Factor-7 / metabolism
  • Interferon-alpha / genetics
  • Interferon-alpha / metabolism*
  • Mutation
  • Paramyxoviridae / genetics
  • Paramyxoviridae / metabolism
  • Paramyxoviridae / physiology
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Toll-Like Receptor 7 / metabolism*
  • Toll-Like Receptor 9 / metabolism*
  • Transcriptional Activation
  • Vero Cells
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*

Substances

  • IRF7 protein, human
  • Interferon Regulatory Factor-7
  • Interferon-alpha
  • TLR9 protein, human
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9
  • Viral Proteins
  • nonstructural C protein, Sendai virus
  • I-kappa B Kinase