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Title: The early pathogenesis of foot-and-mouth disease in cattle after aerosol innoculation: identification of the nasopharynx as the primary site of infection

Author
item Arzt, Jonathan
item Pacheco Tobin, Juan
item Rodriguez, Luis

Submitted to: Veterinary Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/24/2010
Publication Date: 11/1/2010
Citation: Arzt, J., Pacheco Tobin, J., Rodriguez, L.L. 2010. The early pathogenesis of foot-and-mouth disease in cattle after aerosol innoculation: identification of the nasopharynx as the primary site of infection. Veterinary Pathology. 47(6):1048-1063.

Interpretive Summary: The purpose of the current study was to characterize the important steps in virus-host interaction associated with foot-and-mouth disease virus (FMDV) infection of cattle. Steers were experimentally infected with FMDV by a novel aerosol-inoculation method which simulates natural exposure and were subsequently euthanized at various time points after infection. After euthanasia, numerous samples were collected from each steer and screened for live virus, viral RNA, and viral proteins. The most important findings were that the primary sites of infection are the mucosa associated lymphoid regions of the nasopharynx (3-6 hours after inoculation) and that the lungs become infected at somewhat later times (12-24 hours after inoculation). Additionally, it was found that at still later times (24-48 hours after inoculation) FMDV enters the blood stream and causes disseminated disease.

Technical Abstract: In order to characterize the early events of foot–and–mouth disease virus (FMDV) infection in cattle subsequent to simulated natural exposure, steers were aerosol-inoculated with FMDV and euthanized at various times post aerosolization (hpa). Tissues that tested positive for FMDV or viral RNA were examined by immunohistochemistry (IHC) and multi-channel immunofluorescence (MIF) microscopy. All inoculated animals were productively FMDV-infected as confirmed by earliest onsets of detection of FMDV RNA from nasal swabs at 6 hours post aerosolization (hpa), oral swabs at 24 hpa, and serum at 22 hpa. Vesicles were first observed at 48 hours post aerosolization hpa. In previremic steers, FMDV was most consistently localized to nasopharyngeal tissues indicating this region as the most important site of primary viral replication followed by larynx and lungs. The earliest site of microscopic localization of FMDV antigens was the follicle associated epithelium of mucosa – associated lymphoid tissue of the nasopharynx at 6 hpa. At early time points after aerosol inoculation, viral antigens colocalized with cytokeratin-positive pharyngeal epithelial cells; intraepithelial FMDV-negative, MHCII/CD11c-double positive dendritic cells were present in close proximity to FMDV-positive cells. Onset of viremia coincided with marked increase of viral loads in pulmonary tissues and substantial decrease of viral detection in nasopharyngeal tissues. These data indicate that subsequent to aerogenous exposure to FMDV, the temporally defined critical pathogenesis events are establishment of primary infection in the nasopharynx which is followed by establishment of infection in the lungs; viremia is established in a period when viral load is decreasing in the nasopharynx and increasing in the lungs.