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

G. J. Fonseca, G. Thillainadesan, A. F. Yousef, J. N. Ablack, K. L. Mossman, J. Torchia, J. S. Mymryk

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

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.

Original languageBritish English
Pages (from-to)597-606
Number of pages10
JournalCell Host and Microbe
Volume11
Issue number6
DOIs
StatePublished - 14 Jun 2012

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