Inhibition of encephalomyocarditis virus replication by shRNA targeting 1D and 3AB genes in vitro and in vivo

• DOI: 10.1007/s11262-011-0684-7
• Publication Date: 2011-11-03T11:54:45Z
• Authors: Juan Bai; Kangfu Jiang; Basit Zeshan; Xianwei Wang; Yufeng Li; Ping Jiang
• Keywords: Mice, Inbred BALB C; 0303 health sciences; Genes, Viral; Molecular Sequence Data; Brain; Gene Expression; Sequence Analysis, DNA; Viral Load; Virus Replication; Antiviral Agents; Survival Analysis; Cell Line; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Treatment Outcome; Cricetinae; Cardiovirus Infections; Animals; Encephalomyocarditis virus; RNA, Small Interfering; Plasmids

Encephalomyocarditis virus (EMCV) could infect many host species and cause acute myocarditis and sudden death in pre-weaned piglets. It was necessary to develop new antiviral strategies for the treatment of the virus infection. Here, four plasmids expressing shRNA (small hairpin RNA) targeted to 1D or 3AB protein genes of EMCV were constructed and their inhibition efficiency on the replication of EMCV was evaluated in both BHK21 cells and mice. The results showed that three out of those four shRNA constructs could significantly inhibit EMCV replication in BHK21 cells on the levels of viral RNA and protein. Moreover, it was found that the shRNAs could suppress significantly the load of EMCV in the brain tissue of the mice pretreated with the constructs for 6-24 h. The clinical signs and pathological lesions of the mice in the groups inoculated with the shRNA constructed were milder obviously, compared with those in pSUPER-mN3 and challenge control groups. The survival rates of mice inoculated with pSUPER-3AB-1, pSUPER-3AB-2, and pSUPER-1D-1 for 12 h was 100, 80, and 40%, respectively, while, in the control groups it was only 20%. It indicated that the vector-based shRNA targeting to 3AB and 1D genes might be a potential anti-EMCV strategy.