Antiviral, antioxidant, and anti-inflammatory activities of rhein against white spot syndrome virus infection in red swamp crayfish (Procambarus clarkii)

Infection caused by white spot syndrome virus (WSSV) leads to massive mortality and huge economic losses in the crustacean aquaculture industry; however, to date, no effective control means are available to control the disease. Thus, to better understand the pathological aspects of WSSV and to find effective compounds that have the potential to be developed as anti-WSSV agents are imperative. Herein, based on screening of plants with antiviral activity, we found that rhein, an anthraquinone compound in Rheum palmatum L., exhibited strong activity against WSSV infection in a red swamp crayfish (Procambarus clarkii) model. The results showed that rhein could dose dependently inhibit transcription of WSSV ie1, DNApol, and Vp28 genes, reduce viral load in vivo, and significantly improve the survival rate of WSSV-infected crayfish. Through investigation of the mechanisms of action, we found that rhein did not affect the infectivity of viral particles in vitro as well as the entry and release process in vivo. Alternatively, rhein could activate JAK/STAT and NF-kappa B pathways, significantly decrease the expression of crustin-1 and BAF but increase the expression of C-type lectin and proPO to arrest WSSV replication. Moreover, rhein also attenuated WSSV-induced oxidative and inflammatory stresses by regulating the expression of antioxidant and anti-inflammatory-related genes and enhanced innate immunity by reducing total protein levels while increasing the phosphatase activity. Taken together, our study shows rhein as a potent WSSV inhibitor, which provides great potential for the development of prophylaxis and therapy agents for controlling WSSV infection in crustacean aquaculture.

Automated summary

This study identified rhein as a potent inhibitor of WSSV infection in red swamp crayfish. Rhein inhibited viral transcription, reduced viral load, and improved the survival rate of infected crayfish. It activated JAK/STAT and NF-kappa B pathways, decreased the expression of crustin-1 and BAF, and increased the expression of C-type lectin and proPO to arrest WSSV replication. Additionally, rhein attenuated oxidative and inflammatory stresses and enhanced innate immunity. This research provides great potential for the development of prophylaxis and therapy agents for controlling WSSV infection in crustacean aquaculture.