Fig. 8: A model on PWWP3A-mediated inhibition of antiviral innate immune signaling. | Nature Communications

Fig. 8: A model on PWWP3A-mediated inhibition of antiviral innate immune signaling.

From: PWWP3A disrupts the assembly of VISA/MAVS signalosome to inhibit innate immune response against RNA viruses

Fig. 8

Upon binding to viral dsRNA, RIG-I undergoes a conformational change and releases its N-terminal tandem CARD domain, which further recruits to the mitochondrial adaptor protein VISA/MAVS. VISA polymers then recruit TBK1 through different TRAF proteins, which in turn phosphorylates VISA. Phosphorylated VISA recruits IRF3 for phosphorylation through TBK1, consequently inducing the induction of type I IFNs. PWWP3A acts as a binding partner of VISA, thereby specifically inhibiting the recruitment of TBK1-TRAF6 to the VISA signalosome, which further inhibits the IRF3 phosphorylation and IFNs induction following virus infection (i). However, the degree of PWWP3A-mediated inhibition could be regulated by PJA2-mediated PWWP3A degradation after virus infection (ii). Despite a reduction in its overall abundance due to viral infection, PWWP3A still localizes to mitochondria and interacts with VISA to maintain its inhibitory effect.

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