Grass carp (Ctenopharyngodon idella) SIRT3 enhances MAVS-mediated antiviral innate immunity in response to GCRV infection

Grass carp (Ctenopharyngodon idella) is a widely cultivated freshwater fish in the world, which occupies a leading position in China's aquaculture industry. However, the outbreak of hemorrhagic disease resulted from grass carp reovirus (GCRV) infection causes tremendous loss in grass carp production. In this study, we cloned the cDNA of grass carp SIRT3 (gc-SIRT3) and found that it is highly conserved across species and abundantly expressed in grass carp liver. Upon GCRV infection, the expression of gc-SIRT3 is dynamically changed. In addition, grass carp SIRT3 positively regulates the expression of antiviral genes depending on its enzymatic activity. Mechanistically, gc-SIRT3 interacts with gc-MAVS to enhance the MAVS-mediated antiviral response. Furthermore, SIRT3 inhibition in zebrafish or grass carp larvae with the specific inhibitor, 3-TYP, attenuates the antiviral ability against GCRV infection. Our findings may provide clues for understanding the function of SIRT3 in antiviral innate immunity.