Enhanced Antiviral Activity Against Foot-and-Mouth Disease Virus by the Combination of Bovine Type 1 and 2 Interferons

Authors: Moraes, Mauro; Koster, Marla; Grubman, Marvin

Submitted to: American Society for Virology Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 4/12/2007
Publication Date: 7/14/2007
Citation: Moraes, M., Koster, M.J., Grubman, M.J., 2007, Enhanced Antiviral Activity Against Foot-and-Mouth Disease Virus by the Combination of Bovine Type 1 and 2 Interferons. American Society for Virology Meeting. P8-8, P.54

Interpretive Summary:

Technical Abstract: Foot-and-mouth disease virus (FMDV) is the most contagious pathogen of cloven-hoofed animals including swine and bovines. The emergency control of outbreaks is dependent on rapid protection and prevention of spread of the infection. Human adenovirus type 5 expressing porcine interferon alpha (Ad5-pIFN alpha) can partially protect bovines against challenge with FMDV. Interferon (IFN) type 1 and 2 induces antiviral activity against several viruses by overlapping, but different intracellular signaling pathways. Here we show that, in bovines, the combination of type 1 (IFN alpah) and type 2 (IFN gamma) IFN enhanced the antiviral activity against FMDV. In order to demonstrate the possible synergistic effect of bovine IFN alpha (bIFN alpha) and bovine IFN gamma (bIFN gamma), we inoculated groups of 3 bovines with 10^10 pfu of Ad5-boIFN-alpha either alone or in combination with 10^10 pfu Ad5-bIFN gamma as well as 10^10 pfu Ad5-bIFN gamma alone. We also inoculated a group with 10^10 pfu Ad5-Blue as a negative control. Twenty-four hours later, all groups were challenged intradermally with 2x10^4 BID v 50 of FMDV A24. Blood and temperature were taken and clinical examinations were performed daily for the first 7 days after challenge. We also collected serum at 0, 7, 14 and 21 days after challenge. The groups that received one or both Ad5 expressing IFNs were partially protected from challenge with FMDV A24 even though neither antiviral activity nor significant levels of IFNs were detected by ELISA. The group inoculated with Ad5-bIFN gamma had a decrease in the overall clinical score (mean score of 3.33) compared to the negative control group (mean score of 11). In the group receiving bIFN alpha alone, one of three animals had no lesions and the group had a mean clinical score of 2.33 and a delay in the onset of lesions. Finally, in the group receiving both IFNs two of three animals had lesions after challenge (mean score of 2.33), but only one animal had lesions detectable prior to day 8 after challenge. Moreover, there was a 3 or 4 day delay in the onset of the disease in the group treated with both types of IFN compared to the bIFN alpha group and the negative control, respectively. Taken together, the results indicate that the combination of type 1 and 2 IFNs can enhance protection against FMDV in bovines.