Grouper voltage-dependent anion selective channel protein 2 is required for nervous necrosis virus infection

• This is the first report to reveal the role of grouper VDAC2 in NNV infection.
• NNV infection did not considerably affect GVDAC2 gene expression.
• GVDAC2 co-localized but did not directly interact with NNV RdRp at mitochondria.
• ATP level significantly decreased in GVDAC2-downregulated cells.
• Downregulation of GVDAC2 delayed NNV-induced apoptosis.

Nervous necrosis virus (NNV) is a non-enveloped virus with 2 segmented positive-sense single-stranded RNAs. NNV-induced mass mortality has occurred worldwide in many species of cultured marine fish and resulted in substantial economic losses. In our previous study, we cloned the gene of voltage-dependent anion selective channel protein 2 (GVDAC2), and the NNV RNA2 expression level decreased in GVDAC2-knockdown GF-1 cells 24 h after infection. Here, we investigated the role of GVDAC2 in the NNV infection in GF-1 cells. NNV infection did not considerably affect GVDAC2 gene expression. After performing immunostaining, we detected GVDAC2 at the mitochondria and GVDAC2 was colocalized with NNV-RNA-dependent RNA polymerase. However, these 2 proteins did not interact with each other in immunoprecipitation assay. The cellular ATP level in GVDAC2-downregulated cells was lower than that in control cells, and NNV-induced apoptosis was delayed in GVDAC2-siRNA-transfected cells. Therefore, we suggest that GVDAC2 is required for NNV infection for maintaining the cellular ATP level and has positive impact on virus-induced apoptosis.