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Title: Early Events in the Pathogenesis of Foot-and-Mouth Disease in Cattle After Controlled Aerosol Exposure

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

Submitted to: The Veterinary Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/30/2008
Publication Date: 10/16/2008
Citation: Pacheco Tobin, J., Arzt, J., Rodriguez, L.L. 2008. Early Events in the Pathogenesis of Foot-and-Mouth Disease in Cattle After Controlled Aerosol Exposure. The Veterinary Journal. 183(1):46-53.

Interpretive Summary: Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting domestic and wild cloven-hoofed animals. Inhalation of infectious aerosols is generally considered to be the most frequent means of transmission within and between herds of cattle and under appropriate environmental conditions virus-laden droplets may travel vast distances whilst maintaining infectivity. Over the course of greater than 100 years of investigation on FMD, numerous animal inoculation models have been developed to investigate the mechanisms of infection including injecting the virus in the tongue of cattle. Although this method results in clinical disease in most cases, it bypasses many of the important steps in the viral infection. In this study we identified the primary sites of FMDV replication in the cattle using an inoculation method that simulates natural, airborne transmission. Increasing our understanding of the mechanisms of FMD infection will help focus vaccine development, antiviral therapies, and other control measures to minimize the impact of this disease to livestock.

Technical Abstract: The goal of this study was to identify the primary sites of replication of foot-and-mouth disease virus (FMDV) in cattle subsequent to aerogenous inoculation. A novel aerosol inoculation method was developed to simulate natural, airborne transmission and thereby allow the identification of early replication sites. Virus distribution after aerosol inoculation was compared at 24 hours post inoculation (hpi) with simple nasal instillation. Aerosol inoculation of FMDV consistently resulted in virus detection by rRT-PCR and viral isolation in soft palate, pharynx, and lungs with viral antigens also detected by immunohistochemistry in all of these tissues. Aerosolization exposure resulted in typical FMD clinical signs when animals were kept alive long enough to develop disease. This aerosol method is highly reproducible regarding inoculum dose and volume, and allowed the detailed study of early events in FMDV infected cattle. Our extensive post-mortem sampling and trimodal virus detection system allowed a more precise determination of FMDV localization than has been previously reported.