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Title: Enhanced antiviral activity against foot-and-mouth disease virus by the combination of bovine type 1 and 2 interferons

Author
item Moraes, Mauro
item Koster, Marla
item Grubman, Marvin

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 11/1/2006
Publication Date: 11/20/2006
Citation: Moraes, M., Koster, M.J., Grubman, M.J. 2006. Enhanced antiviral activity against foot-and-mouth disease virus by the combination of bovine type 1 and 2 interferons. Sociedade Brasileira de Virology. 74-op. P.74.

Interpretive Summary:

Technical Abstract: Foot-and-mouth disease virus (FMDV) is the most contagious pathogen of cloven-hoofed animals including swine and bovines. In emergency control of outbreaks, it is fundamental to develop rapid protection to prevent spread of the infection. It has been shown that inoculation of 10^10 pfu of human adenovirus type 5 expressing porcine interferon alpha (Ad5-pIFN alpha) partially protects bovines against challenge with FMDV. Interferon (IFN) type 1 and 2 induces antiviral activity against several viruses. This activity is dependent on overlapping, but different intracellular signaling pathways. Here we show that, in bovines, the combination of type 1 (IFN alpha) and type 2 (IFN gamma) IFN enhanced the antiviral activity against FMDV. In order to demonstrate the synergistic effect of bovine IFN alpha (boIFN alpha) and bovine IFN gamma (boIFN gamma) in an animal study, we tested 4 groups of bovines, 3 animals per group, that received 10^10 pfu of Ad5-boIFN-alpha either alone or in combination with 10^10 Ad5- boIFN-gamma as well as 10^10 pfu Ad5-boIFNgamma 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 2 x 10^4 bovine infectious dose 50 of FMDV A24 Cruzeiro. 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. Plasma samples were tested biologically for antiviral activity in MDBK cells against vesicular stomatitis virus and by ELISA for boIFN alpha and boIFN gamma. Viremia and virus in nasal swabs were determined by titration in BHK cells. 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-boIFN gamma had a decrease in the overall clinical score (mean score of 3.33) compared to the negative control group (mean score of 11), but all animals developed clinical disease. In the group receiving Ad5-boIFN 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, but one of these animals only had lesions detectable by 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 boIFN 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.