Inhibition of Foot and Mouth Disease Virus Replication in vitro and in vivo by Dual Short Hairpin RNA-Mediated RNA Interference

Foot and Mouth Disease Virus (FMDV) is one of the most important pathogen to the cattle industry often resulting in severe economic losses. Researchers have reported previously a therapeutic application of plasmid-based shRNA against FMDV but the high degree of sequence diversity between different FMDV serotypes may result in the appearance of escape mutants. In this study, a dual shRNA expression plasmid which can simultaneously express two different shRNA molecules was established and showed stronger inhibitory effects on virus replication than the mixture of two shRNAs. Moreover, the antiviral activity induced by the dual shRNA expression system was aslo evident on other FM-DV serotypes. Therefore, the dual shRNA system targeting two conserved regions of virus genome provides a more powerful strategy for inhibiting FMDV replication in a cross-resistance manner and implicates a potential application in the treatment of high genetic variability of FMDV.