A preliminary study of the pathogenesis of foot-and-mouth disease virus using in situ hybridization.
Five adult guinea pigs were inoculated intraepithelially in the right hindfoot pad with foot-and-mouth disease virus. Animals were euthanatized with carbon dioxide at 4, 10, 24, 48, and 72 hours post-inoculation. Generalized disease developed in the guinea pigs, as evidenced by depression and inappetance by 24 hours post-inoculation and by the formation of vesicles in the noninoculated hindfoot pad by 48 hours post-inoculation. By in situ hybridization, using a 500 base pair biotinylated RNA probe, viral nucleic acid was detected in the noninoculated fore- and hindfoot pads as early as 10 hours post-inoculation, well before any pathologic changes associated with foot-and-mouth disease virus infection were detected. These tissues remained consistently positive for the presence of viral nucleic acid up to the end of the experiment. At this time, in the forefoot pad, even though virus had first been detected with certainty in that tissue 62 hours previously, there was still no microscopic evidence of foot-and-mouth disease virus-induced damage in the histologic section. Similarly, tongue tissue was positive by in situ hybridization at 4, 48, and 72 hours post-inoculation, yet there was never any microscopic evidence of degeneration or vesicle formation. From this preliminary study, it appears that, in the guinea pig, the virus is widely disseminated to foot pads and tongue, with epidermal lesions resulting only in selected areas.