African swine fever virus MGF505-4R facilitates cGAS degradation through TOLLIP-mediated selective autophagy and inhibits the formation of ISGF3 to evade innate immunity.

ABSTRACT: African swine fever virus (ASFV) causes acute and highly lethal disease in pigs. To counteract host defense systems and facilitate virus infection, many ASFV-encoded proteins have regulatory effects on the innate immune response. In this study, we constructed an MGF505-4R-deleted ASFV strain (ASFV-Δ4R) and found that, compared with the wild-type ASFV, ASFV-Δ4R infection significantly increased IFN-β production and elevated the mRNA levels of antiviral genes in porcine alveolar macrophages. Mechanistically, MGF505-4R interacts with cGAS and promotes its degradation by triggering Toll-interacting protein (TOLLIP)-mediated selective autophagy. Specifically, MGF505-4R enhanced the interaction between cGAS and TOLLIP, which subsequently led to increased degradation of cGAS. Additionally, MGF505

SUBMITTER: Yao M 

PROVIDER: S-EPMC12228400 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature