Protective efficacy of adenovirus-mediated small interfering RNAs against encephalomyocarditis virus challenge in mice

Abstract

Encephalomyocarditis virus (EMCV) infection can cause myocarditis and sudden death in pre-weaned piglets and severe reproductive failure in sows. There are no specific antiviral drugs for the treatment of the virus infection. In this study, four recombinant adenoviruses expressing small interfering RNAs (siRNAs) targeting to 1D or 3AB protein genes of EMCV were constructed and their inhibition efficiency on the replication of EMCV was evaluated in both Marc-145 cells and mice. The results showed that the rAd5 expressing siRNAs (rAd5) could inhibit EMCV replication in Marc-145 cells in protein and mRNA levels, as well as the virus yield by approximately 100-1000 times. And the inhibition of viral replication was sustained for 72h and dose-dependent. Animal experiment results showed that EMCV VP1 mRNA level in the brain of mice in the rAd5 groups were obviously lower than those in rAd-G1 and challenge control groups. The virus yields in rAd-1D-2 and rAd-3AB-1 groups were markedly decreased by more than 90.0%. The survival rates of mice in rAd-1D-2 group were significantly higher than those in challenge control groups. Furthermore, the survival mice only showed minor microscopic lesions in brain and minor edema of nerve cell, which was obviously slighter than those in challenge control groups. These results indicated that siRNAs mediated by the adenovirus could provide protective efficacy against EMCV challenge in mice. It might provide a potential strategy for combating EMCV.