Tom70 mediates Sendai virus-induced apoptosis on mitochondria

Virus infection triggers immediate innate immune responses. Apoptosis represents another effective means to restrict virus invasion, besides robust expression of host cytokines and chemokines. IRF3 was recently demonstrated to be indispensable for Sendai virus (SeV)-induced apoptosis, but the underl...

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Bibliographic Details
Published in:Journal of virology 2015-04, Vol.89 (7), p.3804-3818
Main Authors: Wei, Bo, Cui, Ye, Huang, Yuefeng, Liu, Heng, Li, Lin, Li, Mi, Ruan, Kang-Cheng, Zhou, Qin, Wang, Chen
Format: Article
Language:English
Subjects:
Animals
Apoptosis
bcl-2-Associated X Protein - metabolism
Cell Line
Cytochromes c - metabolism
Host-Pathogen Interactions
HSP90 Heat-Shock Proteins - metabolism
Humans
Interferon Regulatory Factor-3 - metabolism
Mice
Mitochondria - physiology
Mitochondrial Membrane Transport Proteins - metabolism
Sendai virus
Sendai virus - physiology
Virus-Cell Interactions
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Summary:Virus infection triggers immediate innate immune responses. Apoptosis represents another effective means to restrict virus invasion, besides robust expression of host cytokines and chemokines. IRF3 was recently demonstrated to be indispensable for Sendai virus (SeV)-induced apoptosis, but the underlying mechanism is not fully understood. Here we report that a dynamic protein complex, Tom70/Hsp90/IRF3/Bax, mediates SeV-induced apoptosis. The cytosolic proapoptotic protein Bax interacts specifically with IRF3 upon virus infection. The mitochondrial outer membrane protein Tom70 recruits IRF3 to mitochondria via Hsp90. Consequently, the relocation of Bax onto mitochondria induces the leakage of cytochrome c into the cytosol and initiates the corresponding apoptosis. Interestingly, IKK-i is essential for this apoptosis, whereas TBK1 is dispensable. Collectively, our study characterizes a novel protein complex that is important for SeV-induced apoptosis. Apoptosis is an effective means of sacrificing virus-infected cells and restraining the spread of virus. In this study, we demonstrate that IRF3 associates with Bax upon virus infection. Tom70 recruits this protein complex to the mitochondrial outer membrane through Hsp90, which thus induces the release of cytochrome c into the cytosol, initiating virus-induced apoptosis. Interestingly, IKK-i plays an essential role in this activation. This study uncovers a novel mechanism of SeV-induced apoptosis.
ISSN:0022-538X
1098-5514
DOI:10.1128/JVI.02959-14