Expression of exogenous IFN-alpha by bypassing the translation block protects cells against FMDV infection.

Abstract

Foot-and-mouth disease virus (FMDV) is the most contagious pathogen of cloven-hoofed animals. Previous studies have demonstrated that type I interferons [alpha/beta interferons (IFN-alpha/betas)] can suppress FMDV replication and spread. Conversely, FMDV can also inhibit IFN-alpha expression in infected cells by blocking cap-dependent translation. To overcome the blockade on IFN-alpha mRNA translation during FMDV infection, we generated an IRES-IFN construct that carries FMDV's internal ribosome entry site (IRES) cDNA sequence between the promoter and porcine IFN-alpha gene. ELISA assays indicated that expression of IFN-alpha regulated by wild-type IRES increased to 125% of pre-infection level after infection for 24h, but the expression of IFN-alpha regulated by nonfunctional IRES mutants were only approximately 50% of pre-infection level. Correspondingly, the former could suppress the replication of FMDV to 20% of the latter and protect cells against FMDV for a longer time. Therefore, these findings provide a new strategy to anti-FMDV therapy.