SNX5 inhibits RLR-mediated antiviral signaling by targeting RIG-I-VISA signalosome.
Upon invading the cell, the viral RNA is recognized by the RIG-I receptor located in the cytoplasm, causing the RIG-I receptor to be activated. The activated RIG-I receptor transmits downstream antiviral signals by interacting with the adaptor protein VISA located on the mitochondria, leading to the production of type ? ... interferons and crude inflammatory cytokine genes. Although there have been many studies on antiviral signal transduction of RIG-I receptors in recent years, the mechanism of RIG-I-VISA-mediated antiviral regulation is still not fully understood. In this study, we identified SNX5 as a negative regulator of RLR-mediated antiviral signaling. Our results show that overexpression of SNX5 inhibits viral-induced activation of the IFN-? promoter, ISRE, NF-?B, and IRF3, whereas RNAi knockdown of SNX5 expression shows opposite results. We also found that overexpression of SNX5 enhanced RIG-I's K48 ubiquitination and attenuated its K63 ubiquitination, resulting in inhibition of virus-induced RIG-I expression. Besides, further studies show that SNX5 overexpression weakens the interaction between VISA and TRAF2/5. Our findings suggest that SNX5 negatively regulates RLR-mediated antiviral signaling by targeting the RIG-I-VISA signalosome and provide new evidence for the negative regulation of RIG-I-mediated innate immune response mechanisms.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Antiviral Agents, DEAD Box Protein 58, Gene Knockout Techniques, HEK293 Cells, Humans, Sendai virus, Signal Transduction, Sorting Nexins, Tumor Necrosis Factor Receptor-Associated Peptides and Proteins, Ubiquitination
Adaptor Proteins, Signal Transducing, Antiviral Agents, DEAD Box Protein 58, Gene Knockout Techniques, HEK293 Cells, Humans, Sendai virus, Signal Transduction, Sorting Nexins, Tumor Necrosis Factor Receptor-Associated Peptides and Proteins, Ubiquitination
Biochem Biophys Res Commun
Date: Dec. 19, 2019
PubMed ID: 31806368
View in: Pubmed Google Scholar
Download Curated Data For This Publication
226198
Switch View:
- Interactions 6