Overexpression of Bcl2 and Bcl2L1 Can Suppress Betanodavirus-Induced Type III Cell Death and Autophagy Induction in GF-1 Cells

Betanodavirus infection induces viral nervous necrosis (VNN) in fish. However, the role of cell death and autophagy in the pathogenesis of VNN remains unknown. This study aimed to investigate the effect of red-spotted grouper nervous necrosis virus (RGNNV) infection on Bcl2 downregulation and overexpression on asymmetric interaction between cell death and autophagy. The mRFP-LC3 reporter system was used to identify autophagosome formation in GF-1 (Grouper fin-1) fish cells. We found that the RGNNV could strongly induce autophagosome formation 36 h post-infection (hpi) after autophagy inhibitor 3-MA had downregulated anti-apoptotic genes such as Bcl2 and Bcl2L1 (Bcl-xL). We proposed that the overexpression of Bcl2 and Bcl2L1 can modulate both cell death and autophagy. Then, we found that it can also reduce either type III cell death or autophagy, which are mildly correlated with reduced viral replication. Our data suggest that RGNNV-induced Bcl2 downregulation correlates with the asymmetrical interaction between cell death induction and the autophagy process, which resembles viral replication.

Automated summary

This study investigates the effect of red-spotted grouper nervous necrosis virus (RGNNV) infection on the asymmetrical interaction between cell death and autophagy. The results show that RGNNV infection can induce autophagosome formation and the overexpression of Bcl2 and Bcl2L1 can modulate both cell death and autophagy. Furthermore, the downregulation of Bcl2 is correlated with the induction of cell death and the autophagy process.