The NS1 protein of influenza A virus blocks RIG-I-mediated activation of the noncanonical NF-κB pathway and p52/RelB-dependent gene expression in lung epithelial cells

J Virol. 2012 Sep;86(18):10211-7. doi: 10.1128/JVI.00323-12. Epub 2012 Jul 11.

Abstract

Influenza A virus (IAV) infection of epithelial cells activates NF-κB transcription factors via the canonical NF-κB signaling pathway, which modulates both the antiviral immune response and viral replication. Since almost nothing is known so far about a function of noncanonical NF-κB signaling after IAV infection, we tested infected cells for activation of p52 and RelB. We show that the viral NS1 protein strongly inhibits RIG-I-mediated noncanonical NF-κB activation and expression of the noncanonical target gene CCL19.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / antagonists & inhibitors*
  • DEAD-box RNA Helicases / metabolism
  • Epithelial Cells / metabolism
  • Epithelial Cells / virology
  • Gene Expression
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology
  • Host-Pathogen Interactions / physiology
  • Humans
  • Influenza A virus / pathogenicity
  • Influenza A virus / physiology*
  • Lung / metabolism
  • Lung / virology
  • NF-kappa B / metabolism*
  • NF-kappa B p52 Subunit / metabolism
  • Receptors, Immunologic
  • Signal Transduction
  • Transcription Factor RelB / metabolism
  • Viral Nonstructural Proteins / physiology*

Substances

  • INS1 protein, influenza virus
  • NF-kappa B
  • NF-kappa B p52 Subunit
  • RELB protein, human
  • Receptors, Immunologic
  • Viral Nonstructural Proteins
  • Transcription Factor RelB
  • RIGI protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases