Inhibition of L-deleted foot-and-mouth disease virus replication by alpha/beta interferon involves double-stranded RNA-dependent protein kinase

We previously demonstrated that the ability of foot-and-mouth disease virus (FMDV) to form plaques in cell culture is associated with the suppression of alpha/beta interferon (IFN-alpha/beta). In the present study, we used Es cherichia coli-expressed porcine and bovine IFN-alpha or -beta individually to demonstrate that each was equally effective in inhibiting FMDV replicat ion. The block in FMDV replication appeared to be at the level of protein t ranslation, suggesting a role for double-stranded RNA-dependent protein kin ase (PKR), In support of these findings, treatment of porcine and bovine ce lls with 2-aminopurine, an inhibitor of PKR, increased the yield of virus 8 .8- and 11.2-fold, respectively, compared to that in untreated infected cel ls. In addition, results of FMDV infection in mouse embryonic fibroblast ce lls derived from gene knockout mice lacking the gene for RNase L-/- or PKR- /- or both indicated an important role for PKR in the inhibition of FMDV re plication.