|De Los Santos, Teresa|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 4/11/2006
Publication Date: 7/15/2006
Citation: Grubman, M.J., De Los Santos, T., Koster, M.J., Turecek, T.E., Wang, H., Andryev, V., Moraes, M.P. 2006. Enhanced antiviral activity against foot-and-mouth disease virus by a combination of type 1 and 2 porcine interferons. American Society of Virology Annual Meeting. 2006. P. 150.
Technical Abstract: Foot-and-mouth disease virus (FMDV) is the most contagious pathogen of cloven-hoofed animals including swine and bovines and it is essential that after an outbreak rapid protection measures are initiated to prevent spread of the disease. Previously, we showed that inoculation of swine with 109 pfu of human adenovirus type 5 expressing porcine interferon alpha (Ad5-pIFN'alpha) can protect animals when they are challenged with FMDV one day later. Type 1 and 2 IFNs have antiviral activity against many viruses. We examined the possible synergistic antiviral effects of pIFN'alpha and pIFN gamma (pIFN gamma) against FMDV in cell culture and in an animal study. A synergistic effect of type 1 and 2 IFNs was evident in swine cells. We were able to detect an increased inhibition of plaque formation and reduction in virus yield by combinations of pIFN'alpha and pIFN'gamma proteins as compared with either alone. In addition, analysis of a limited set of host genes from treated cells by real-time RT-PCR revealed an increased induction of some of these genes with the combination IFN treatment. In the animal study, six groups of swine were inoculated with Ad5-pIFN'alpha and Ad5-IFN'gamma alone or in combination. After 24 hours all groups were challenged intradermally with FMDV A24 Cruzeiro. The groups that received Ad5s expressing both IFNs and the group inoculated with the high dose of Ad5-pIFN'gamma'alone were completely protected from challenge with FMDV and had no viremia, while the groups inoculated with Ad5-pIFN'alpha or a low dose of Ad5-pIFN'gamma alone and the negative control group had clinical disease and viremia. By immunoprecipitation and ELISAs for viral nonstructural (NS) proteins the animals that developed lesions had detectable antibodies against NS proteins, while the animals in the protected groups did not. We were, however, unable to detect antiviral activity or significant levels of IFNs in the protected groups, but did detect an enhanced expression of the same host genes as identified in the cell culture study. Taken together, the results indicate that the combination of type 1 and 2 IFNs act synergistically against FMDV in vitro and in vivo.