Adenovirus evasion of interferon-mediated innate immunity by direct antagonism of a cellular histone posttranslational modification.
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.
Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.
G J
GJ
Fonseca
G
G
Thillainadesan
A F
AF
Yousef
J N
JN
Ablack
K L
KL
Mossman
J
J
Torchia
J S
JS
Mymryk
D017500:Adenovirus E1A Proteins / Q000378:metabolism; D000260:Adenoviruses, Human / Q000276:immunology* / Q000472:pathogenicity*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D007372:Interferons / Q000037:antagonists & inhibitors*; D011499:Protein Processing, Post-Translational; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination
D017500:Adenovirus E1A Proteins; D006657:Histones; D025801:Ubiquitin; D007372:Interferons; C506646:RNF20 protein, human; D044767:Ubiquitin-Protein Ligases