Contact challenge of cattle with foot-and-mouth disease virus validates the role of the nasopharyngeal epithelium as the site of primary and persistent infection.

Authors: STENFELDT, CAROLINA - University Of Minnesota; Smoliga, George; Hartwig, Ethan; PALINSKI, RACHEL - Kansas State University; FISH, IAN - Oak Ridge Institute For Science And Education (ORISE); SILVA, EDIANE - Oak Ridge Institute For Science And Education (ORISE); Pauszek, Steven; Arzt, Jonathan

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/27/2018
Publication Date: 12/12/2018
Citation: Stenfeldt, C., Smoliga, G.R., Hartwig, E.J., Palinski, R., Fish, I.H., Silva, E.B., Pauszek, S.J., Arzt, J. 2018. Contact challenge of cattle with foot-and-mouth disease virus validates the role of the nasopharyngeal epithelium as the site of primary and persistent infection. Scientific Reports. https://doi.org/10.1128/mSphere.00493-18.
DOI: https://doi.org/10.1128/mSphere.00493-18

Interpretive Summary: Foot-and-mouth disease (FMD) is an important infectious disease that limits global trade in animal products. To better understand how foot-and-mouth disease virus (FMDV) infects cattle, an experimental model was developed in which cattle were exposed to pigs that had been inoculated with the virus. It was shown that exposure to the infected pigs led to FMDV infection of the upper respiratory tract of both vaccinated and non-vaccinated cattle. The vaccinated cattle did not develop any clinical signs of disease, but the virus was still detectable in tissues and secretions from these animals for up to 35 days. In the non-vaccinated cattle, the virus spread through the body and caused vesicular lesions (blisters) in the mouth and on the feet. After recovery from the clinical stage of disease, these animals were still carriers of infectious virus in their upper respiratory tract. Analysis of the virus genome by deep sequencing techniques provided additional and novel information of differences in how the virus amplifies in different tissues of infected animals. This information will help protect US livestock herds from outbreaks of FMD.

Technical Abstract: The pathogenesis of foot-and-mouth disease virus (FMDV) in cattle was investigated through early and late stages of infection by use of an optimized experimental model for controlled contact exposure. Time-limited exposure of cattle to FMDV-infected pigs led to primary FMDV infection of the nasopharyngeal mucosa in both vaccinated and non-vaccinated cattle. In non-vaccinated cattle, the infection generalized rapidly, without apparent virus amplification in the lungs prior to establishment of viremia and systemic disease, while vaccinated cattle were protected against clinical disease and viremia. However, all vaccinated cattle were sub-clinically infected, and persistent infection occurred at similarly high prevalence in both animal cohorts. Infection dynamics in cattle were consistent and synchronous, and comparable to conventional systems of needle inoculation. However, the current experimental model utilizes a natural route of virus exposure and is thus suitable for investigations of disease pathogenesis and host response. Deep sequencing of viruses obtained during early infection of pigs and cattle indicated that virus populations sampled from sites of primary infection were markedly more diverse than viruses from vesicular lesions of cattle, suggesting the occurrence of substantial bottlenecks associated with vesicle formation. These data expand previous knowledge of FMDV pathogenesis in cattle and provide novel insights for validation of inoculation models of bovine FMD studies.