IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging MAVS and TBK1.

Intracellular RNA viruses are sensed by receptors retinoic acid-inducible gene I/MDA5, which trigger formation of the mitochondrial antiviral signaling (MAVS) complex on mitochondria. Consequently, this leads to the activation of TNFR-associated factor family member-associated NF-κB activator-binding kinase 1 (TBK1) and phosphorylation of IFN regulatory factor 3 (IRF3). It remains to be elucidated how MAVS activates TBK1/IRF3.

Mitochondrial ubiquitin ligase MARCH5 promotes TLR7 signaling by attenuating TANK action.

The signaling of Toll-like receptors (TLRs) is the host's first line of defense against microbial invasion. The mitochondrion is emerging as a critical platform for antiviral signal transduction. The regulatory role of mitochondria for TLR signaling remains to be explored.

Tom70 mediates activation of interferon regulatory factor 3 on mitochondria.

Intracellular RNA viruses are sensed by receptors retinoic acid-inducible gene 1 (RIG-I)/melanoma differentiation-associated gene 5 (MDA5) that trigger the formation of MAVS signal complex on mitochondria. Consequently, this leads to the activation of TANK-binding kinase 1 (TBK1) and phosphorylation of interferon regulatory factor 3 (IRF3), both of which constitutively associate with cytosolic chaperone Hsp90. It remains largely unknown how MAVS activates TBK1/IRF3.

Positive regulation of interferon regulatory factor 3 activation by Herc5 via ISG15 modification.

Virus infection induces host antiviral responses, including induction of type I interferons. Transcription factor interferon regulatory factor 3 (IRF3) plays a pivotal role and is tightly regulated in this process. Here, we identify HERC5 (HECT domain and RLD 5) as a specific binding protein of IRF3 by immunoprecipitation.

TRIM21 is essential to sustain IFN regulatory factor 3 activation during antiviral response.

Virus infection induces host antiviral responses including induction of type I IFNs. Transcription factor IFN regulatory factor 3 (IRF3) plays an essential role and is tightly regulated in this process. Herein we report that TRIM21 (tripartite motif-containing 21) is significantly induced and interacts with IRF3 upon RNA virus infection.

Study on substrate specificity at subsites for severe acute respiratory syndrome coronavirus 3CL protease.

Autocleavage assay and peptide-based cleavage assay were used to study the substrate specificity of 3CL protease from the severe acute respiratory syndrome coronavirus. It was found that the recognition between the enzyme and its substrates involved many positions in the substrate, at least including residues from P4 to P2'. The deletion of either P4 or P2' residue in the substrate would decrease its cleavage efficiency dramatically.

A novel auto-cleavage assay for studying mutational effects on the active site of severe acute respiratory syndrome coronavirus 3C-like protease.

The 3C-like protease (3CLpro) of severe acute respiratory syndrome (SARS) has been proposed as an attractive target for drug design. His41 and Cys145 were essential for the active site as the principal catalytic residues. In this study, we mutated the two sites, expressed four resulting mutants in Escherichia coli and characterized.