ATG5 negatively regulates grass carp reovirus-induced immune-inflammatory response by degrading RIG-I and MDA5

Grass carp reovirus (GCRV) is a highly virulent pathogen responsible for hemorrhagic disease in grass carp, leading to devastating losses in aquaculture. The study reveals that GCRV triggers an acute immune-inflammatory response in young grass carp, which is linked to high mortality, while a milder immune response occurs in older, resistant fish. Importantly, the autophagy-related gene ATG5 was identified as a critical regulator that suppresses excessive immune-inflammatory responses by promoting the degradation of RIG-I and MDA5, two key viral sensors. ATG5 not only reduces viral replication but also limits IRF7 phosphorylation, a key step in interferon signaling. This research uncovers a novel mechanism by which autophagy moderates viral-induced immune response, suggesting that ATG5 could be a valuable target for therapeutic interventions aimed at controlling GCRV infection and preventing cytokine storms in aquaculture. These findings could have broader implications for managing viral infections in fish farming.