African swine fever virus MGF505-3R inhibits cGAS-STING-mediated IFN-β pathway activation by degrading TBK1

Abstract African swine fever virus (ASFV) is an important pathogen causing acute infectious disease in domestic pigs and wild boars that seriously endangers the global industry. As ASFV structurally complex encodes a large number of functional proteins, no effective vaccine has been developed to date. Thus, dissecting mechanisms immune escape induced by proteins crucial. A previous study showed ASFV-encoded protein factor host immunity. In this study, we identified negative regulator, MGF505-3R, significantly downregulated cGAS/STING- poly (dG:dC)-mediated IFN-β interferon stimulation response element (ISRE) reporter activity suppressed IFNB1 IFIT2 mRNA levels. addition, TBK1, IRF3 IκBα phosphorylation levels were also inhibited. Mechanistically, MGF505-3R interacted with cGAS/TBK1/IRF3 targeted TBK1 for degradation, thereby disrupting cGAS-STING-mediated signaling pathway, which appears be highly correlated autophagy. Knockdown expression enhanced IL-1β production. Taken together, our revealed regulatory mechanism involving MGF505-3R-cGAS-STING axis provided insights into evasion strategy employed involves autophagy innate pathways.