Fish promotes viral products by modulating the innate immune response and exosomal machinery.

Viral nervous necrosis caused by the nervous necrosis virus (NNV) poses a significant threat to the global aquaculture industry. Developing preventive methods to minimize economic losses due to NNV infections is crucial. This study explored the role of the sorting nexin 27 () gene, encoded by the orange-spotted grouper () and referred to as , as an immune regulator affecting red-spotted grouper nervous necrosis virus (RGNNV) infection . Our findings revealed that negatively regulates interferon (IFN)-related cytokines and the promoter activities of fish ISRE and NF-κB. Furthermore, we identified the SNX-FERM and SNX-FERM-like domains as responsible for the interaction between and RGNNV coat protein. Through the detection of viable virions associated with -containing exosomes, we propose that may contribute to the release process of RGNNV by influencing the apoptosis-linked gene 2-interacting protein X (ALIX)-associated exosomal pathway. Consequently, our study suggests that promotes RGNNV replication by inhibiting the IFN immune response and facilitating virus production and release through ALIX-mediated exosomal machinery.IMPORTANCERed grouper nervous necrosis virus (RGNNV), a member of the family, has emerged as a significant cause of fish diseases worldwide, leading to high morbidity and mortality rates. This study investigated the sorting nexin 27 () gene encoded by the orange-spotted grouper () on RGNNV infection in grouper kidney cells. Our findings revealed that negatively regulated the interferon pathway, resulting in the promotion of RGNNV replication. Additionally, we observed that could interact with apoptosis-linked gene 2-interacting protein X (ALIX) and the RGNNV coat protein, suggesting its potential involvement in viral release processes through modulation of the exosomal pathway. Our study identified as a key target that RGNNV exploits to enhance viral production. This finding offers valuable insights into the immune evasion and viral release mechanisms of non-enveloped RNA viruses.