Adenovirus Evasion of Interferon-Mediated Innate Immunity by Direct Antagonism of a Cellular Histone Posttranslational Modification Journal Articles uri icon

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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.

authors

  • Fonseca, GJ
  • Thillainadesan, G
  • Yousef, AF
  • Ablack, JN
  • Mossman, Karen
  • Torchia, J
  • Mymryk, JS

publication date

  • June 2012