Viral apoptosis is induced by IRF-3-mediated activation of Bax

Saurabh Chattopadhyay, Joao Trindade Marques, Michifumi Yamashita, Kristi L Peters, Kevin Smith, Avanti Desai, Bryan Raymond George Williams, Ganes C Sen

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Abstract

Upon infection with many RNA viruses, the cytoplasmic retinoic acid inducible gene-I (RIG-I) pathway activates the latent transcription factor IRF-3, causing its nuclear translocation and the induction of many antiviral genes, including those encoding interferons. Here, we report a novel and distinct activity of IRF-3, in virus-infected cells, that induces apoptosis. Using genetically defective mouse and human cell lines, we demonstrated that, although both pathways required the presence of RIG-I, IPS1, TRAF3 and TBK1, only the apoptotic pathway required the presence of TRAF2 and TRAF6 in addition. More importantly, transcriptionally inactive IRF-3 mutants, such as the one missing its DNA-binding domain, could efficiently mediate apoptosis. Apoptosis was triggered by the direct interaction of IRF-3, through a newly identified BH3 domain, with the pro-apoptotic protein Bax, their co-translocation to the mitochondria and the resulting activation of the mitochondrial apoptotic pathway. Thus, IRF-3 is a dual-action cytoplasmic protein that, upon activation, translocates to the nucleus or to the mitochondrion and triggers two complementary antiviral responses of the infected cell.
Original languageEnglish
Pages (from-to)1762 - 1773
Number of pages12
JournalThe EMBO Journal
Volume29
Issue number10
DOIs
Publication statusPublished - 2010

Cite this

Chattopadhyay, S., Marques, J. T., Yamashita, M., Peters, K. L., Smith, K., Desai, A., Williams, B. R. G., & Sen, G. C. (2010). Viral apoptosis is induced by IRF-3-mediated activation of Bax. The EMBO Journal, 29(10), 1762 - 1773. https://doi.org/10.1038/emboj.2010.50