TRAF 3 IP 3 mediates the recruitment of TRAF 3 to MAVS for antiviral innate immunity

Abstract

RIG‐I‐MAVS antiviral signaling represents an important pathway to stimulate interferon production and confer innate immunity to the host. Upon binding to viral RNA and Riplet‐mediated polyubiquitination, RIG‐I promotes prion‐like aggregation and activation of MAVS. MAVS subsequently induces interferon production by activating two signaling pathways mediated by TBK1‐IRF3 and IKK‐NF‐κB respectively. However, the mechanism underlying the activation of MAVS downstream pathways remains elusive. Here, we demonstrated that activation of TBK1‐IRF3 by MAVS‐Region III depends on its multimerization state and identified TRAF3IP3 as a critical regulator for the downstream signaling. In response to virus infection, TRAF3IP3 is accumulated on mitochondria and thereby facilitates the recruitment of TRAF3 to MAVS for TBK1‐IRF3 activation. Traf3ip3‐deficient mice demonstrated a severely compromised potential to induce interferon production and were vulnerable to RNA virus infection. Our findings uncover that TRAF3IP3 is an important regulator for RIG‐I‐MAVS signaling, which bridges MAVS and TRAF3 for an effective antiviral innate immune response.

DUSP11-mediated control of 5′-triphosphate RNA regulates RIG-I sensitivity

“…4), DUSP11-deficient mice display reduced viral loads (∼3.3-fold reduction in viral transcript) in the spleen (Fig. 6G), on par with what has been reported for some other factors associated with the antiviral response (Wang et al 2019;Zhu et al 2019). Notably, we observed a greater magnitude of this effect in the female DUSP11-deficient mice (∼5.1-fold for females as compared with ∼1.6fold for males) (Supplemental Fig.…”

TRIM24 facilitates antiviral immunity through mediating K63-linked TRAF3 ubiquitination

“…The cells were cultured at 37°C under 5% CO 2 in DMEM supplemented with 10% FBS, 100 U/ml penicillin, and 100 µg/ml streptomycin. SeV, VSV, VSV-GFP, and HSV-1 were also kindly provided by F. Hou ( Zhu et al, 2019a ).…”

“…Virus titer assay Viral titer was determined by using a plaque assay as previously described (Zhu et al, 2019a). In brief, HEK293T cells in 6-well plates were infected with serial dilutions of the recovered VSV for 1 h. The infected cells were overlaid with 1% soft agar dissolved in DMEM and incubated for 48 h. Plates were stained with 0.1% crystal violet in DMEM to display plaques, which were then quantitated.…”

Adaptive changes in the genomes of wild rabbits after 16 years of viral epidemics

“…Thirty-two of the SNPs were within 40 kb distance to 57 known genes. While 12 of these candidate genes have not been functionally characterized as yet, the majority have known functions in antiviral immune responses, apoptosis or other disease responses (Bokoch, 2005;Gibbs, Roelants, & O'Bryan, 2008;Zhu et al, 2019, see supplement for further information). Apoptosis of hepatocytes was found to be induced during RHD (Jung, Lee, Tai, Park, & Lee, 2000;Niedźwiedzka-Rystwej & Deptuła, 2012).…”