Evaluation on the antiviral activity of ribavirin against Micropterus salmoides rhabdovirus (MSRV) in vitro and in vivo

Abstract

Micropterus salmoides rhabdovirus (MSRV) causes a severe lethal infection in largemouth bass fry, resulting in great economic loss. However, there is no effective drug to control this viral infection. In this study, a screening assay based on real-time quantitative PCR (RT-qPCR) was firstly performed, and the results showed that ribavirin exhibited the best antiviral activity, with a 48 h-IC50 (inhibitory concentration at half-maximal activity) of 1.21 μM and significantly reduced the viral titer at 24 h post infection (P < 0.01). Furthermore, ribavirin protected the MSRV-infected cells against CPE (cytopathic effect) and nuclear damage, and significantly increased cell viability after this virus infection (P < 0.05). In addition, a series of four assays were performed in order to evaluate the potential mechanism of ribavirin against MSRV infection in GCO cells. Our results indicated that ribavirin reduced the infectivity of MSRV, repressed early virus replication and inhibited release of the viral particles. Finally, the data from two in vivo assays showed that ribavirin had a significant preventive effect against MSRV infection in largemouth bass. A single intraperitoneal administration of 100 mg/kg ribavirin at 4 days before the viral challenge increased the survival rate of largemouth bass by 30%, and significantly reduced viral loads in the liver, spleen and kidney of fish (P <0.01). Besides, the survival rate of largemouth bass orally administrated with 100 mg/kg ribavirin was improved significantly at 4 days post MSRV infection (P < 0.05), and the viral load in the liver, spleen, and kidney was also decreased significantly during 5 days post the infection (P < 0.01). Overall, ribavirin exhibited a good antiviral effect against MSRV infection both in vitro and in vivo, and this finding may provide a reference for discovery and development of anti-MSRV drugs in aquaculture.