Fish TOLLIP manipulates ATG5 for autophagic degradation of STING to attenuate antiviral interferon responses.

ABSTRACT: While robust interferon (IFN) responses in fish are critical for viral clearance, dysregulated signalling can trigger detrimental hyperinflammation, necessitating precise immunoregulatory mechanisms. This study identified Toll-interacting protein (TOLLIP) as a pivotal negative regulator of IFN production in grass carp (Ctenopharyngodon idella). Upon grass carp reovirus (GCRV) infection, TOLLIP expression increases significantly in tissues and cells. Furthermore, TOLLIP overexpression reduced GCRV- and polyinosinic-polycytidylic acid (poly I:C)-induced IFN expression, whereas tollip knockdown increased the cellular IFN production capacity. TOLLIP subsequently binds and degrades STING. Further mechanistic studies revealed that TOLLIP degrades STING in a dose-dependent manner via an autophagy

SUBMITTER: Tian MZ 

PROVIDER: S-EPMC12449016 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature