The pathogenesis of persistent foot-and-mouth disease virus (FMDV) infection was investigated in 46 cattle that were either naiveor had been vaccinated using a recombinant, adenovirus-vectored vaccine 2 weeks before challenge. The prevalence of FMDVpersistence was similar in both groups (62% in vaccinated cattle, 67% in nonvaccinated cattle), despite vaccinated cattle havingbeen protected from clinical disease. Analysis of antemortem infection dynamics demonstrated that the subclinical divergencebetween FMDV carriers and animals that cleared the infection had occurred by 10 days postinfection (dpi) in vaccinated cattleand by 21 dpi in nonvaccinated animals. The anatomic distribution of virus in subclinically infected, vaccinated cattle was restrictedto the pharynx throughout both the early and the persistent phases of infection. In nonvaccinated cattle, systemicallydisseminated virus was cleared from peripheral sites by 10 dpi, while virus selectively persisted within the nasopharynx of a subsetof animals. The quantities of viral RNA shed in oropharyngeal fluid during FMDV persistence were similar in vaccinated andnonvaccinated cattle. FMDV structural and nonstructural proteins were localized to follicle-associated epithelium of the dorsalsoft palate and dorsal nasopharynx in persistently infected cattle. Host transcriptome analysis of tissue samples processed bylaser capture microdissection indicated suppression of antiviral host factors (interferon regulatory factor 7, CXCL10 [gammainterferon-inducible protein 10], gamma interferon, and lambda interferon) in association with persistent FMDV. In contrast,during the transitional phase of infection, the level of expression of IFN-mRNA was higher in follicle-associated epithelium ofanimals that had cleared the infection. This work provides novel insights into the intricate mechanisms of FMDV persistenceand contributes to further understanding of this critical aspect of FMDV pathogenesis.
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© 2016 Stenfeldt et al.