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

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• 作者：G.J. Fonseca¹ ; G. Thillainadesan² ; A.F. Yousef¹ ; J.N. Ablack¹ ; K.L. Mossman⁴ ; J. Torchia² ; ³ ; ⁵ ; J.S. Mymryk¹ ; ³ ; ⁵ ; ^{jmymryk@uwo.ca}
• 刊名：Cell Host Microbe
• 出版年：2012
• 期刊代码：P58_19313128
• 类别：imm
• 出版时间：14 June, 2012
• 卷：11
• 期：6
• 页码：597-606
• 文件大小：1214 K

摘要

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Summary

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聽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.