Antiviral therapy in shrimp through plant virus VLP containing VP28 dsRNA against WSSV.

Santiago Ramos-Carreño,Ruben D Cadena-Nava,Ricardo Valencia-Yañez,Jaime Ruiz-Garcia,Ivone Giffard-Mena,Maria Teresa Viana,Alfredo Nuñez-Rivera,Jose N Zamudio-Ocadiz

doi:10.3762/bjoc.17.95

Abstract

The white spot syndrome virus (WSSV), currently affecting cultured shrimp, causes substantial economic losses to the worldwide shrimp industry. An antiviral therapy using double-stranded RNA interference (dsRNAi) by intramuscular injection (IM) has proven the most effective shrimp protection against WSSV. However, IM treatment is still not viable for shrimp farms. The challenge is to develop an efficient oral delivery system that manages to avoid the degradation of antiviral RNA molecules. The present work demonstrates that VLPs (virus-like particles) allow efficient delivery of dsRNAi as antiviral therapy in shrimp. In particular, VLPs derived from a virus that infects plants, such as cowpea chlorotic mottle virus (CCMV), in which the capsid protein (CP) encapsidates the dsRNA of 563 bp, are shown to silence the WSSV glycoprotein VP28 (dsRNAvp28). In experimental challenges in vivo, the VLPs- dsRNAvp28 protect shrimp against WSSV up to 40% by oral administration and 100% by IM. The novel research demonstrates that plant VLPs, which avoid zoonosis, can be applied to pathogen control in shrimp and also other organisms, widening the application window in nanomedicine.

Highlights

The white spot syndrome virus (WSSV) is recognized as one of the most severe epidemic pathogens of shrimp, causing severe economic losses to shrimp aquaculture
The antiviral response of RNA interference (RNAi) is triggered by double-stranded RNA to block the synthesis of a specific viral protein, in the case of WSSV the targets being the structural proteins VP19, VP24, VP26, and VP28, as they are involved in cell recognition, virus entry, binding and assembly of the virion
The double-stranded RNA (dsRNA) was efficiently encapsidated with chlorotic mottle virus (CCMV) capsid protein (CP) using a mass ratio of 6:1 of CP/dsRNAvp28

Summary

Introduction

The white spot syndrome virus (WSSV) is recognized as one of the most severe epidemic pathogens of shrimp, causing severe economic losses to shrimp aquaculture. The RNAi mechanism comprises a set of cellular processes of posttranscriptional gene silencing that begins with administering the double-stranded RNA (dsRNA). It concludes with a specific gene silencing based on sequence homology between the digested fragments of the dsRNA and the gene of interest [12-16]. The antiviral response of RNAi is triggered by double-stranded RNA (dsRNA) to block the synthesis of a specific viral protein, in the case of WSSV the targets being the structural proteins VP19, VP24, VP26, and VP28, as they are involved in cell recognition, virus entry, binding and assembly of the virion. The VP28 glycoprotein plays an important role in systemic infection by interacting with cell membrane proteins, and it is one of the most abundant proteins along with VP26 (≈60%) in the external WSSV surface [21,22]

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