C-myc modulates the replication of RGNNV via glutamine-mediated ATP production in grouper fin cells

C-myc is a proto-oncogene that plays an important role in a variety of diseases.There were a lot of research on the correlation between C-myc and human viruses.However,the study about C-myc related to aquatic species virus is very limited.In the present study,the qRT-PCR,cellular immunofluorescence and western blotting determination data reported that C-myc and glutaminase(GLS)genes were significantly upregulated when grouper fin cells(GF-1)were infected with red grouper nervous necrosis virus(RGNNV).After knocking down the C-myc gene,the mRNA and protein levels of GLS,capsid protein(CP)and RNA polymerase(RdRp)of RGNNV were significantly reduced in RGNNV-infected GF-1 cells and the overexpression of the C-myc gene remarkably promoted these genes,which indicated that the replication of the virus and GLS gene were positively regulated by C-myc in RGNNV-infected GF-1 cells.In addition,supplementation of exogenous ATP can partially restore viral replication when RGNNV-infected GF-1 cells were cultured in glutamine-free medium,which confirmed that the glutamine was decomposed into ATP to provide energy for viral replication.Further studies confirmed that overexpression of C-myc can increase the content of ATP in normal cells.To sum up,these data suggested that activation of C-myc gene affected viral replication by regulating GLS expression to drive glutamine dissolution.