Kinetic control of nervous necrosis virus by cell-derived antiviral substance and metabolic state in fish cell lines.

Abstract

Nervous necrosis virus (NNV) causes high mortality in many fish species. We previously reported that sevenband grouper fin (SeGF) cells persistently infected with NNV (PI-SeGF) produce a small-molecule, antiviral substance that suppresses NNV multiplication and cellular metabolic activity. In this study, we investigate the kinetics of NNV multiplication, cellular metabolic rate and production of antiviral substance in striped snakehead (SSN-1), SeGF and PI-SeGFcells at culture temperatures of 17-32&#xa0;&#xb0;C. Our results demonstrated that the NNV multiplication rate reached a maximum of 2.0 logfold/day and was more closely associated with cellular metabolic rate rather than culture temperature. In SeGF and PI-SeGFcells, antiviral substance production increased with rising metabolic activity, and its accumulation, in turn, suppressed both cellular growth and viral multiplication. Notably, when the NNV multiplication rate was suppressed to <1.5 logfold/day in SeGF cells, the maximum viral titer remained below 10TCID/ml. In contrast, when the antiviral response was insufficient, the viral titer increased to &#x2265; 10TCID/ml. SSN-1&#xa0;cells cultured at < 28&#xa0;&#xb0;C produced little to no antiviral substance, resulting in consistently high viral yields regardless of culture temperature. These findings suggest that the kinetics of NNV multiplication are controlled by the balance between production of antiviral substance and cellular metabolic rate rather than temperature alone. This mechanistic insight may help explain how low-temperature exposure or persistent infection can control the multiplication of viruses in fish and devise strategies to combat viral infections in the aquaculture industry.