Submitted to: Journal of Interferon and Cytokine Research
Publication Type: Peer reviewed journal
Publication Acceptance Date: 3/27/2003
Publication Date: 4/1/2003
Citation: WU, Q., BRUM, M.C., CARON, L., KOSTER, M.J., GRUBMAN, M.J. ADENOVIRUS-MEDIATED TYPE I INTERFERON EXPRESSION PARTIALLY PROTECTS CATTLE FROM FOOT-AND-MOUTH DISEASE. JOURNAL OF INTERFERON AND CYTOKINE RESEARCH. v23: 359-368, 2003. Interpretive Summary: Foot-and-mouth disease virus (FMDV) causes an economically devastating disease of cloven-hoofed animals including swine and cattle. Vaccines produced by chemical inactivation of virus are available, but there are concerns about their safety and they do not induce protection prior to about 7 days postvaccination. In the event of an FMD outbreak in a disease-free country such as the US, it is necessary to induce immediate protection. We have shown that in cell culture FMDV is inhibited by type I interferon. We have developed a recombinant human adenovirus as an expression vector that contains the gene for interferon alpha. We have previously demonstrated that swine given one inoculation of this recombinant virus and then challenged with virulent FMDV one day postinoculation were completely protected from clinical signs of disease and challenge virus replication. To extend these studies to cattle, animals were inoculated with the recombinanat virus and challenged either one or two days postinoculation. Control noninoculated animals developed severe clinical disease, while recombinant virus inoculated animals developed disease later and clinical signs were significantly less severe as compared to the control animals. One of the inoculated animals never developed vesicular lesions. These results indicate that cattle inoculated with the recombinant virus containing interferon alpha are partially protected from FMD.
Technical 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-alpha/beta) as a novel anti-FMD agent. We have previously demonstrated that swine inoculated with replication-defective human adenovirus type 5 (Ad5) vector expressing porcine IFN-alpha (Ad5-pIFN alpha) were completely protected from FMD virus (FMDV) challenge. To extend this approach to bovines, we constructed Ad5 vectors which express bovine IFN-alpha or -beta (Ad5-bIFNalpha and Ad5-bIFN beta). Cells infected with these viruses produced high levels of biologically active bIFN alpha/beta; however, despite expression in vitro, no detectable IFN-induced biological activity was found in cattle inoculated with Ad5-bIFN alpha. Since pIFN-alpha inhibits FMDV replication in bovine cells, we evaluated the potential use of pIFN-alpha against FMD in cattle. In cattle inoculated with Ad5-pIFN alpha, the appearance of vesicles was delayed after challenge with FMDV and disease was less severe than in control animals. One Ad5-pIFN alpha inoculated animal never developed clinical disease. Similarly, although all the Ad5-pIFN alpha inoculated animals developed viremia, it was delayed for 1 day as compared to the control group. These results suggest that in vivo expression of pIFN-alpha partially protected cattle from FMD.