title: Venezuelan equine encephalitis replicon particles can induce rapid protection against foot-and-mouth disease virus.
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 10(7) or 10(8) 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.
authors.affiliation: Plum Island Animal Disease Center, North Atlantic Area, Agricultural Research Service, US Department of Agriculture, Greenport, New York, USA.
authors.forename: Fayna
authors.initials: F
authors.lastname: Diaz-San Segundo
authors.forename: Camila C A
authors.initials: CC
authors.lastname: Dias
authors.forename: Mauro P
authors.initials: MP
authors.lastname: Moraes
authors.forename: Marcelo
authors.initials: M
authors.lastname: Weiss
authors.forename: Eva
authors.initials: E
authors.lastname: Perez-Martin
authors.forename: Gary
authors.initials: G
authors.lastname: Owens
authors.forename: Max
authors.initials: M
authors.lastname: Custer
authors.forename: Kurt
authors.initials: K
authors.lastname: Kamrud
authors.forename: Teresa
authors.initials: T
authors.lastname: de los Santos
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Grubman
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics*; D005536:Foot-and-Mouth Disease / Q000276:immunology / Q000517:prevention & control*; D029544:Foot-and-Mouth Disease Virus / Q000276:immunology*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D016898:Interferon-alpha / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016019:Survival Analysis
chemical_list: D016898:Interferon-alpha