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Title: Porcine Interferon Gamma Promotes a Protective Innate Immune Response Against Foot-and-Mouth Disease in Swine

item Moraes, Mauro
item De Los Santos, Teresa
item Pacheco Tobin, Juan
item Koster, Marla
item Turecek, Traci
item Golde, William
item 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: Diaz-San Segundo, F., Moraes, M., De Los Santos, T., Pacheco Tobin, J., Koster, M.J., Turecek, T.E., Dawson, H., Golde, W.T., Grubman, M.J. 2007 Porcine Interferon Gamma Promotes a Protective Innate Immune Response Against Foot-and-Mouth Disease in Swine. American Society for Virology Meeting. W20-3, P. 30

Interpretive Summary:

Technical Abstract: We have recently demonstrated that the synergistic action of type I and II interferons (IFN) can rapidly protect swine against challenge with a low dose of foot-and-mouth disease virus (FMDV). While we did not detect antiviral activity or the presence of IFN alpha or gamma in any of the protected animals, there was an up-regulation of some IFN stimulated genes (ISGs), including IP-10 and INDO in peripheral blood mononuclear cells(PBMC). IP-10 is involved in the recruitment of T cells and natural killer cells to sites of infection causing a rapid innate response to a variety of viruses. To gain a more comprehensive understanding of the mechanism of protection stimulated by IFNs we have expanded this initial study to characterize, 1. ISGs induced in PBMCs and skin from the heel bulb, a site of FMDV replication, after vaccination and challenge and 2. cell types recruited to the site of challenge. Four groups of pigs were inoculated with different combinations of IFN using an adenovirus vector (Ad5): 10^8 pfu Ad5-pIFN alpha in combination with 10^9 or 10^10 pfu Ad5-pIFN gamma (low and high combination groups), 10^10 pfu Ad5-pIFN gamma alone, and 10^10 pfu of a control Ad5 virus. One day later all groups were challenged with a high dose of FMDV. The control and low combination groups developed viremia starting at 1 days postchallenge (dpc), although the low combination group had delayed and less severe clinical disease. The group that received pIFN gamma alone and the high combination group showed a delay in the appearance of viremia and significantly reduced clinical disease. One animal inoculated with the high dose of IFN gamma did not develop lesions or have virus in skin biopsies even at the inoculation site at 1 dpc and the other two animals only developed lesions at 5-6 dpc. All IFN vaccinated pigs showed a mild lymphopenia 1 dpc and a recovery the day after except for the animals inoculated with pIFN gamma alone which required 3 days. We are currently examining the induction of a number of ISGs in both PBMCs and skin. Despite the high challenge dose and the stress caused by multiple biopsies, our results imply that IFN gamma has an important role in inducing a protective innate immune response against FMDV challenge.