Topic：The mechanisms of immune evasion by pathogens
Guests：Dr. Dapeng Yan Researcher Fudan University
Time：2019.12.30 pm 14:00-15:00
Venue：meeting room 518 of Medical school
【 Abstract 】
HIV-1 infection-induced cGAS–STING–TBK1–IRF3 signaling transduction activates innate immunity to produce type I interferon (IFN). The HIV-1 non-structural protein, viral infectivity factor (Vif) is essential for HIV-1 replication by degrading the host restriction factor APOBEC3G, but whether and how it regulates host immune response remain unknown. Here we show that Vif inhibited HIV-1-induced production of type I IFN. HIV-1 infection induced the activation of host tyrosine kinase FRK, which subsequently phosphorylated the immunoreceptor tyrosine-based inhibitory motif (ITIM) of Vif and enhanced Vif’s interaction with the cellular tyrosine phosphatase SHP-1 to inhibit type I IFN. Mechanistically, the association of Vif with SHP-1 facilitated SHP-1 recruitment to STING and inhibited K63-linked ubiquitination of STING at Lys337 by dephosphorylating STING at Tyr162. These findings reveal a previously unknown mechanism by which HIV-1 evades antiviral immunity through the ITIM-containing protein to inhibit the post-translational modification of STING and provide a molecular basis for developing new therapeutics to treat HIV-1 infection.