Mangiferin and Taurine Ameliorate MSRV Infection by Suppressing NF-κB Signaling

The emergence or reemergence of viruses pose a substantial threat and challenge to the world population, livestock, and wildlife. However, the landscape of antiviral agents either for human or animal viral diseases is still underdeveloped. The far tougher actuality is the case that there are no approved antiviral drugs in the aquaculture industry, although there are diverse viral pathogens. In this study, using a novel epithelial cell line derived from the brain of Micropterus salmoides (MSBr), inflammation and oxidative stress were found to implicate the major pathophysiology of M. salmoides rhabdovirus (MSRV) through transcriptome analysis and biochemical tests. Elevated levels of proinflammatory cytokines (interleukin-1 beta [IL-1 beta], IL-6, IL-8, tumor necrosis factor alpha [TNF-alpha], and gamma interferon [IFN-gamma]) and accumulated contents of reactive oxygen species (ROS) as well as biomarkers of oxidative damage (protein carbonyl and 8-OHdG) were observed after MSRV infection in the MSBr cells. Mangiferin or taurine dampened MSRV-induced inflammation and rescued the oxidative stress and, thus, inhibited the replication of MSRV in the MSBr cells with 50% effective concentration (EC50) values of 6.77 mu g/mL and 8.02 mg/mL, respectively. Further, mangiferin or taurine hampered the activation of NF-kappa B1 and the NF-kappa B1 promoter as well as the increase of phosphorylated NF-kappa B (p65) protein level induced by MSRV infection, indicating their antiviral mechanism by suppressing NF-kappa B signaling. These findings exemplify a practice approach, aiming to dampen and redirect inflammatory responses, to develop broad-spectrum antivirals. IMPORTANCE Aquaculture now provides almost half of all fish for human food in 2021 and plays a significant role in eliminating hunger, promoting health, and reducing poverty. There are diverse viral pathogens that decrease production in aquaculture. We developed a novel epithelial cell line derived from the brain of Micropterus salmoides, which can be used for virus isolation, gene expressing, and drug screening. In this study, we focus on M. salmoides rhabdovirus (MSRV) and revealed its pathophysiology of inflammation and oxidative stress. Aiming to dampen and redirect inflammatory responses, mangiferin or taurine exhibited their antiviral capability by suppressing NF-kappa B signaling. Our findings exemplify a practice approach to develop broad-spectrum antivirals by dampening and redirecting inflammatory responses.

Automated summary

The emergence or reemergence of viruses poses a significant threat and challenge to the world population, livestock, and wildlife. However, the development of antiviral agents for viral diseases in humans and animals is still lacking. This study focused on the pathophysiology of M. salmoides rhabdovirus (MSRV) and identified inflammation and oxidative stress as major factors. Mangiferin or taurine showed potential as antiviral agents by suppressing NF-kappa B signaling and reducing inflammation and oxidative stress.