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 Escherichia coli-expressed porcine and bovine IFN-alpha or -beta individually to demonstrate that each was equally effective in inhibiting FMDV replication. The block in FMDV replication appeared to be at the level of protein translation, suggesting a role for double-stranded RNA-dependent protein kinase (PKR). In support of these findings, treatment of porcine and bovine cells 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 cells. In addition, results of FMDV infection in mouse embryonic fibroblast cells 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 replication.
Chinsangaram
J
J
Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Greenport, New York 11944, USA.
Koster
M
M
Grubman
M J
MJ
D000818:Animals; D005537:Aphthovirus / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D002417:Cattle; D002460:Cell Line; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004722:Endoribonucleases / Q000378:metabolism; D005536:Foot-and-Mouth Disease / Q000821:virology; D005816:Genetic Complementation Test; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000378:metabolism; D013552:Swine; D014779:Virus Replication / Q000187:drug effects*
D016898:Interferon-alpha; D012330:RNA, Double-Stranded; D016899:Interferon-beta; D011494:Protein Kinases; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; D010450:Endopeptidases; C088747:leader proteinase, foot-and-mouth disease virus