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Title: Infection dynamics of foot-and-mouth disease virus in pigs using two novel simulated natural inoculation methods

Author
item STENFELDT, CAROLINA - Oak Ridge Institute For Science And Education (ORISE)
item Pacheco Tobin, Juan
item Rodriguez, Luis
item Arzt, Jonathan

Submitted to: Research in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/26/2014
Publication Date: 2/1/2014
Publication URL: http://handle.nal.usda.gov/10113/59449
Citation: Stenfeldt, C., Pacheco Tobin, J., Rodriguez, L.L., Arzt, J. 2014. Infection dynamics of foot-and-mouth disease virus in pigs using two novel simulated natural inoculation methods. Research in Veterinary Science. 96:396-405.

Interpretive Summary: Foot-and-mouth disease virus causes a devastating disease of pigs, cattle and other clovenhoofed animals. Because the virus can easily change, it is critical to routinely test vaccines to make sure they are effective. Having reproducible animal models to test vaccines is critical to make sure vaccines are adequate against outbreak strains. Two newly developed techniques for induction of foot-and-mouth disease (FMD) in pigs were evaluated for their potential to provide a simulated natural infection model for use in experimental studies. The dynamics of infection generated through direct deposition of virus in the upper respiratory tract (intra-nasopharyngeal inoculation; INP) or in the upper gastrointestinal tract (intra-oropharyngeal inoculation; IOP) were investigated using either of two strains of FMD virus at varying doses. The IOP route consistently caused disease more reproducibly than the INP route. The utility of the IOP inoculation system was further demonstrated through comparison to a more commonly used system of needle inoculation (intradermal heel bulb inoculation) in a vaccine-challenge experiment. It is concluded that the novel system of IOP inoculation, offers a valid alternative to traditionally used systems for FMDV inoculation of pigs, applicable for experimental studies of FMDV pathogenesis and vaccine development.

Technical Abstract: In order to characterize foot-and-mouth disease virus (FMDV) dynamics in pigs, two simulated-natural inoculation systems were developed and evaluated using two different strains of FMDV (O1-Manisa and A24-Cruzeiro) at varying doses. Direct intra-oropharyngeal (IOP) and intra-nasopharyngeal (INP) inoculation both enabled precise control of dose and timing of inoculation while emulating field exposure conditions. There were substantial differences in the outcomes of the two inoculation routes. IOP inoculation resulted in consistent and synchronous infection, for both virus strains investigated, with viral RNA detectable in serum and swabs from 24- 48 hours post infection (hpi) and clinical lesions appearing at 48-72 hpi. INP inoculation of FMDV O1 Manisa at low or medium doses resulted in delayed, or completely absent clinical infection, whereas high dose inoculation with this virus caused fulminant FMD. Dose-dependence was less marked amongst pigs inoculated with FMDV A24 Cruzeiro in that all pigs developed clinical FMD, although with a delayed onset following INP inoculation. All pigs that developed clinical infection (regardless of inoculation route) had detectable levels of FMDV RNA in their oropharynx directly following inoculation. Furthermore, FMDV antigens were localized by immunomicroscopy to the oropharyngeal tonsils suggesting a role in early infection of pigs. The utility of the IOP inoculation system was further demonstrated through comparison to intradermal heel bulb inoculation in a vaccine-challenge experiment. Thus, the novel system of IOP inoculation described herein, offers a valid alternative to traditionally used systems for FMDV inoculation of pigs, applicable for experimental studies of FMDV pathogenesis and vaccinology.