Adenovirus-mediated type I interferon expression delays and reduces disease signs in cattle challenged with foot-and-mouth disease virus.
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-alpha/beta) 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-alpha (Ad5-PoIFN-alpha) were completely protected from FMD virus (FMDV) challenge. To extend this approach to bovines, we constructed Ad5 vectors that express bovine IFN-alpha or IFN-beta (Ad5-BoIFN-alpha and Ad5-BoIFN-beta). Cells infected with these viruses produced high levels of biologically active BoIFN-alpha/beta, but despite expression in vitro, no detectable IFN-induced biologic activity was found in cattle inoculated with Ad5-BoIFN-alpha. Because PoIFN-alpha inhibits FMDV replication in bovine cells, we evaluated the potential use of PoIFN-alpha against FMD in cattle. In cattle inoculated with Ad5-PoIFN-alpha, the appearance of vesicles was delayed after challenge with FMDV and disease was less severe than in control animals. One Ad5-PoIFN-alpha-inoculated animal never developed clinical disease. Similarly, although all the Ad5-PoIFN-alpha-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-alpha partially protected cattle from FMD.
D000256:Adenoviridae / Q000235:genetics*; D000257:Adenoviridae Infections; D000818:Animals; D002417:Cattle; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005536:Foot-and-Mouth Disease / Q000517:prevention & control*; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics*; D005822:Genetic Vectors; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000502:physiology*; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D013552:Swine; D013997:Time Factors; D014612:Vaccines
D007370:Interferon Type I; D014612:Vaccines