Inhibition of L-Deleted Foot-and-Mouth Disease Virus Replication by Alpha/Beta Interferon Involves Double-Stranded RNA-Dependent Protein Kinase

Abstract

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-␣/␤). In the present study, we used Escherichia coli-expressed porcine and bovine IFN-␣ or -␤ 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.

African Swine Fever Virus Multigene Family 360 and 530 Genes Affect Host Interferon Response

“…IFN antiviral activity was assayed biologically with vesicular stomatitis virus (VSV) in Madin-Darby bovine kidney cells (MDBK) cells as previously described (6,7). Briefly, supernatants of noninfected and ASFV-infected macrophages were collected, clarified by high-speed centrifugation (35,000 ϫ g, 1 h), acidified at pH 2, and neutralized with NaOH.…”

Venezuelan Equine Encephalitis Replicon Particles Can Induce Rapid Protection against Foot-and-Mouth Disease Virus

“…These results demonstrated that IP-10 plays a critical role in the IFN-induced protection against FMDV although presumably other ISGs may also be involved in inhibition of FMDV replication. As mentioned before, we have previously demonstrated in cell culture that PKR and the OAS/RNase L system control FMDV replication (6,28). It will be useful to examine the role of additional ISG products in this process.…”

“…Disease was followed (A), and serum samples were collected for 7 days after challenge to assay for viremia (B). Serum of mice was tested for antiviral activity (C) and presence of IFN-␣ (D) at different time points (3,6, and 24 h) after VRP-GFP treatment before FMDV challenge. *, P Յ 0.05; **, P Յ 0.01; ***, P Յ 0.001. mice and PBS-treated IP-10 KO or WT mice (Fig.…”

“…Serum samples of mice inoculated with VRP-GFP at different time points (3,6, and 24 h) were collected, and antiviral activity was tested in L929 cells as previously described (20). Briefly, serum samples were diluted 1:10 in medium and acidified to pH 2.0 for 24 h. Following neutralization to pH 7.4, the samples were titrated by 2-fold dilutions and added to confluent monolayers of L929 cells.…”

“…To address the need of protecting vaccinated animals during this window of susceptibility, we have used an approach that induces the innate immune response. We have shown that FMDV replication is inhibited by prior treatment of cells with interferon type I (IFN-␣/␤), II, or III (6)(7)(8). Based on this information, we constructed Ad5 vectors containing porcine type I IFN genes (Ad5-poIFN-␣/␤) and demonstrated that swine inoculated with Ad5-poIFN-␣/␤ are protected from challenge with FMDV A24 Cruzeiro as early as 1 day after Ad5-poIFN-␣/␤ administration (4,9,10).…”