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Novel antiviral therapeutics to control foot-and-mouth disease

Dias, Camila C., Moraes, Mauro P., Weiss, Marcelo, Diaz-San Segundo, Fayna, Perez-Martin, Eva, Salazar, Andres M., de los Santos, Teresa, Grubman, Marvin J.
Journal of Interferon and Cytokine Research 2012 v.32 no.10 pp. 462
Foot-and-mouth disease virus, animal diseases, cell culture, disease control, double-stranded RNA, foot-and-mouth disease, gene expression, gene induction, genes, immunity, interferon-alpha, mononuclear leukocytes, oligonucleotides, swine, therapeutics, vaccines
Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. Vaccines require approximately 7 days to induce protection, thus prior to this time vaccinated animals are still susceptible to the disease. Our group has previously shown that swine inoculated with 1x10^11 focus forming units (FFU) of a replication-defective human adenovirus containing the gene for porcine interferon alpha (Adt-pIFN alpha) are sterilely protected from FMDV serotypes A24, O1 Manisa or Asia 1 when the animals are challenged 1 day post administration and protection can last for 3-5 days. Poly ICLC is a synthetic double stranded RNA that is a viral mimic and activates multiple innate immune pathways through interaction with TLR-3 and MDA-5. It is a potent inducer of IFNs. In this study, we initially examined the effect of poly IC and IFN-alpha on FMDV replication and gene induction in cell culture. Poly ICLC alone or combined with Adt-pIFN alpha was then evaluated for its therapeutic efficacy in swine against intradermal challenge with FMDV A24, 1 day post treatment. Groups of swine were subcutaneously inoculated with poly ICLC alone (4 or 8 mg) or in combination with different doses of Adt-pIFN alpha (2.5x10^9, 1x10^9 or 2.5x10^8 FFU). While different degrees of protection were achieved in all the treated animals, a dose of 8 mg of poly ICLC alone or combined with 1x10^9 FFU of Adt-pIFN alpha was sufficient to sterilely protect swine when challenged 24 h later with FMDV A24. IFN stimulated gene (ISG) expression in peripheral blood mononuclear cells at 1 day post treatment was broader and higher in protected animals than in non-protected animals. These data indicate that poly ICLC is a potent stimulator of IFN and ISGs in swine and at an adequate dose is sufficient to induce complete protection against FMD.