Enterovirus 71 2C Protein Inhibits NF-κB Activation by Binding to RelA(p65)

Sci Rep. 2015 Sep 23;5:14302. doi: 10.1038/srep14302.

Abstract

Viruses evolve multiple ways to interfere with NF-κB signaling, a key regulator of innate and adaptive immunity. Enterovirus 71 (EV71) is one of primary pathogens that cause hand-foot-mouth disease. Here, we identify RelA(p65) as a novel binding partner for EV71 2C protein from yeast two-hybrid screen. By interaction with IPT domain of p65, 2C reduces the formation of heterodimer p65/p50, the predominant form of NF-κB. We also show that picornavirus 2C family proteins inhibit NF-κB activation and associate with p65 and IKKβ. Our findings provide a novel mechanism how EV71 antagonizes innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Enterovirus A, Human / metabolism*
  • Enzyme Activation
  • HEK293 Cells
  • Humans
  • I-kappa B Kinase / metabolism
  • Immune Evasion / immunology*
  • Immune Evasion / physiology
  • NF-kappa B p50 Subunit / metabolism*
  • Protein Binding / physiology
  • Saccharomyces cerevisiae / genetics
  • Transcription Factor RelA / metabolism*
  • Two-Hybrid System Techniques
  • Viral Nonstructural Proteins / metabolism*

Substances

  • Carrier Proteins
  • NF-kappa B p50 Subunit
  • Transcription Factor RelA
  • Viral Nonstructural Proteins
  • I-kappa B Kinase
  • 2C protein, viral