Abstract
Virus infection induces the MAVS-TNFR-associated factor (TRAF) 3 signaling axis on mitochondria. It remains to elucidate the corresponding regulatory processes. In this study, we identify UXT-V1 as a novel TRAF3-binding protein. UXT-V1 is critical for the virus-induced activation of NF-κB and IFN regulatory factor 3. Reduction of UXT-V1 impairs the induction of IFN-β and attenuates the host antiviral responses. The N-terminal TRAF-binding motif of UXT-V1 binds to the C-terminal TRAF domain of TRAF3, thus facilitating the interaction between TRAF3 and MAVS. Notably, TRAF3 and TNFR-associated death domain protein are recruited onto mitochondria upon virus infection. These translocations are blocked when knocking down UXT-V1. Thus, UXT-V1 represents a novel integral component of the MAVS signalosome on mitochondria, mediating the innate antiviral signal transduction.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / immunology*
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Adaptor Proteins, Signal Transducing / metabolism
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Amino Acid Motifs
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Animals
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Cell Cycle Proteins
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HEK293 Cells
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HeLa Cells
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Humans
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Interferon Regulatory Factor-3 / genetics
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Interferon Regulatory Factor-3 / immunology
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Interferon Regulatory Factor-3 / metabolism
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Interferon-beta / genetics
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Interferon-beta / immunology
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Interferon-beta / metabolism
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Mice
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Mitochondria / genetics
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Mitochondria / immunology*
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Mitochondria / metabolism
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Molecular Chaperones / genetics
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Molecular Chaperones / immunology*
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Molecular Chaperones / metabolism
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NF-kappa B / genetics
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NF-kappa B / immunology
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NF-kappa B / metabolism
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NIH 3T3 Cells
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Neoplasm Proteins / genetics
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Neoplasm Proteins / immunology*
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Neoplasm Proteins / metabolism*
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Protein Binding
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Signal Transduction / genetics
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Signal Transduction / immunology*
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TNF Receptor-Associated Factor 3 / genetics
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TNF Receptor-Associated Factor 3 / immunology
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TNF Receptor-Associated Factor 3 / metabolism
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Virus Diseases / genetics
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Virus Diseases / immunology*
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Virus Diseases / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Cell Cycle Proteins
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IPS-1 protein, mouse
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IRF3 protein, human
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Interferon Regulatory Factor-3
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Irf3 protein, mouse
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MAVS protein, human
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Molecular Chaperones
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NF-kappa B
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Neoplasm Proteins
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TNF Receptor-Associated Factor 3
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UXT protein, human
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UXT protein, mouse
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Interferon-beta