PATHOGENESIS OF WILD-TYPE AND LEADERLESS FOOT-AND-MOUTH-DISEASE VIRUSIN CATTLE

Four calves were experimentally infected via aerosol with foot-and-mou th disease virus. Two were infected with a wild-type virus derived fro m a full-length infectious clone (A12-IC), and two were infected with a clone-derived virus lacking the leader gene (A12-LLV2), with euthana sia and tissue collection at 24 and 72 h postexposure (hpe). Clinical disease was apparent only in the animal given A12-IC and euthanized at 72 hpe. In situ hybridization revealed that the animal infected with A12-IC and euthanized at 24 hpe had abundant viral nucleic acid in the lung, present in clusters of positive tells in the respiratory bronch iolar epithelium and associated subepithelial regions. At 72 hpe in th e A12-IC-infected calf, viral nucleic acid in the lung was present in interstitial areas, and in addition, viral nucleic acid was detectable in epithelial tissues around histologically apparent vesicles. In ani mals infected with A12-LLV2, viral nucleic acid was detectable in the lung at both 24 and 72 hpe, but staining revealed a more localized dis tribution with less nucleic acid than was found in animals given A12-I C. Therefore, it appears that after aerosol exposure to A12-IC, early replication is in the region of the lung, with subsequent disseminatio n to distal sites, In comparison, the A12-LLV2 virus is much less wide ly disseminated in the lung at 24 hpe, with no lesions or virus detect able in secondary sites at 72 hpe. The greatly reduced pathogenicity o f A12-LLV2 may make it an excellent candidate for a modified live vira l vaccine.