Adenovirus evasion of interferon-mediated innate immunity by direct antagonism of a cellular histone posttranslational modification

Cell Host Microbe. 2012 Jun 14;11(6):597-606. doi: 10.1016/j.chom.2012.05.005.

Abstract

Overcoming the cellular type I interferon (IFN) host defense response is critical for a virus to ensure successful infection. Investigating the effects of human adenovirus (HAdV) infection on global cellular histone posttranslational modification (hPTM), we discovered that virus infection-induced activation of IFN signaling triggers a global increase in the monoubiquitination of histone 2B (H2B) at lysine 120, which is a mark for transcriptionally active chromatin. This hPTM, catalyzed by the hBre1/RNF20 complex, is necessary for activation of the cellular IFN-stimulated gene (ISG) expression program in response to viruses. To establish effective infection, the HAdV E1A protein binds to and dissociates the hBre1 complex to block IFN-induced H2B monoubiquitination and associated ISG expression. Together, these data uncover a key role for H2B monoubiquitination in the type I IFN response and a viral mechanism of antagonizing this hPTM to evade the IFN response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenovirus E1A Proteins / metabolism
  • Adenoviruses, Human / immunology*
  • Adenoviruses, Human / pathogenicity*
  • Histones / metabolism*
  • Humans
  • Immune Evasion*
  • Immunity, Innate
  • Interferons / antagonists & inhibitors*
  • Protein Processing, Post-Translational*
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination

Substances

  • Adenovirus E1A Proteins
  • Histones
  • Ubiquitin
  • Interferons
  • RNF20 protein, human
  • Ubiquitin-Protein Ligases