Adenovirus-Mediated Type I Interferon Expression Delays and Reduces Disease Signs in Cattle Challenged with Foot-and-Mouth Disease Virus

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Abstract
Foot-and-mouth disease (FMD) is an economically important disease of livestock. Eliminating FMD outbreaks in previously disease-free countries often relies on restriction of animal movement and massive slaughter of infected and in-contact susceptible animals. To develop a more effective and humane FMD control strategy, we explored the possibility of using type I interferon (IFN-α/β) as a novel anti-FMD agent. We have demonstrated previously that swine inoculated with replication-defective human adenovirus type 5 (Ad5) vector expressing porcine IFN-α (Ad5-PoIFN-α) were completely protected from FMD virus (FMDV) challenge. To extend this approach to bovines, we constructed Ad5 vectors that express bovine IFN-α or IFN-β (Ad5-BoIFN-α and Ad5-BoIFN-β). Cells infected with these viruses produced high levels of biologically active BoIFN-α/β, but despite expression in vitro, no detectable IFN-induced biologic activity was found in cattle inoculated with Ad5-BoIFN-α. Because PoIFN-α inhibits FMDV replication in bovine cells, we evaluated the potential use of PoIFN-α against FMD in cattle. In cattle inoculated with Ad5-PoIFN-α, the appearance of vesicles was delayed after challenge with FMDV and disease was less severe than in control animals. One Ad5-PoIFN-α-inoculated animal never developed clinical disease. Similarly, although all the Ad5-PoIFN-α-inoculated animals developed viremia, it was delayed for 1 day as compared with the control group. These results suggest that in vivo expression of PoIFN-α partially protected cattle from FMD.