RACK1 degrades MAVS to promote bovine ephemeral fever virus replication via upregulating E3 ubiquitin ligase STUB1

SARS-CoV-2 ORF10 suppresses the antiviral innate immune response by degrading MAVS through mitophagy

“…By screening adapter proteins in the RLR signaling pathway, we identified MAVS as the target via which ORF10 suppresses the IFN-I signaling pathway. At present, the negative posttranslational regulation of MAVS is thought to be achieved mainly by K48-linked ubiquitination [ 35 ], blockade of signal transduction, and autophagy [ 46 ]. In ORF10-expressing HeLa cells, treatment with CQ or Baf A1 but not MG132 reversed the ORF10-mediated inhibition of MAVS expression, indicating that ORF10 degrades MAVS through the autophagy pathway.…”

“…All enzymes used for cloning procedures were purchased from Vazyme (Nanjing, China). The HA-MDA5, Flag-RIG-IN, Flag-MAVS, IRF3 (5D)-HA, TBK1-HA, and IFN-β-Luc plasmids and the pRL-TK internal control luciferase reporter plasmid used in the study were described previously [ 34 , 35 ]. SARS-CoV-2 ORF10 was cloned into pEGFP-N1 (Clontech Laboratories, Mountain View, CA), GFP-LC3 was cloned into pcDNA3.1 (Clontech Laboratories, Mountain View, CA), ORF10 was cloned into pCMV-HA (Clontech Laboratories, Mountain View, CA), Flag-NIX was cloned into pLVX-IRES-Puro (Clontech Laboratories, Mountain View, CA), and pcDNA3.1-mCherry-GFP-LC3 (mCherry-GFP-LC3) was purchased from Miaoling.…”

Post-Translational Modifications of Proteins in Cytosolic Nucleic Acid Sensing Signaling Pathways

“…RNA viruses also hijack MAVS degradation mechanisms to facilitate viral replication and viral infection. For example, RNA viral infection enhances the expression of RACK1 (Receptors for activated C kinase 1), by upregulating the expression of the E3 ligase STUB1 (STIP1 homology and U-box containing protein 1) to target MAVS for ubiquitination and degradation; RACK1 facilitates BEFV (bovine epidemic fever virus) replication ( 169 ).…”