Venezuelan Equine Encephalitis Replicon Particles Can Induce Rapid Protection against Foot-and-Mouth Disease Virus

Authors

Fayna Diaz-San Segundo, Plum Island Animal Disease Center
Camila C. A. Dias, Plum Island Animal Disease Center
Mauro P. Moraes, University of Connecticut
Marcelo Weiss, Plum Island Animal Disease Center
Eva Perez-Martin, Plum Island Animal Disease Center
Gary Owens, AlphaVax, Research Triangle Park
Max Custer, AlphaVax, Research Triangle Park
Kurt Kamrud, AlphaVax, Research Triangle Park
Teresa de los Santos, Plum Island Animal Disease Center
Marvin J. Grubman, Plum Island Animal Disease CenterFollow

Document Type

Article

Date of this Version

5-2013

Citation

Journal of Virology 87(10) May 2013 (5447–5460); doi:10.1128/JVI.03462-12

Abstract

We have previously shown that delivery of the porcine type I interferon gene (poIFN-α/β) with a replication-defective human adenovirus vector (adenovirus 5 [Ad5]) can sterilely protect swine challenged with foot-and-mouth disease virus (FMDV) 1 day later. However, the need of relatively high doses of Ad5 limits the applicability of such a control strategy in the livestock industry. Venezuelan equine encephalitis virus (VEE) empty replicon particles (VRPs) can induce rapid protection of mice against either homologous or, in some cases, heterologous virus challenge. As an alternative approach to induce rapid protection against FMDV, we have examined the ability of VRPs containing either the gene for green fluorescent protein (VRP-GFP) or poIFN-α (VRP-poIFN- α) to block FMDV replication in vitro and in vivo. Pretreatment of swine or bovine cell lines with either VRP significantly inhibited subsequent infection with FMDV as early as 6 h after treatment and for at least 120 h posttreatment. Furthermore, mice pretreated with either 10⁷ or 10⁸ infectious units of VRP-GFP and challenged with a lethal dose of FMDV 24 h later were protected from death. Protection was induced as early as 6 h after treatment and lasted for at least 48 h and correlated with induction of an antiviral response and production of IFN- α. By 6 h after treatment several genes were upregulated, and the number of genes and the level of induction increased at 24 h. Finally, we demonstrated that the chemokine IP-10, which is induced by IFN- α and VRP-GFP, is directly involved in protection against FMDV.