A Preliminary Study of the Pathogenesis of Foot-and-mouth Disease Virus Using in situ Hybridization

Abstract

Abstract. Five adult guinea pigs were inoculated intraepithelially in the right hindfoot pad with foot-andmouth disease virus. Animals were euthanati zed with carbon dioxide at 4, 10, 24, 48, and 72 hours postinoculation. 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 postinoculation. 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 IO 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.

Skin as a potential source of infectious foot and mouth disease aerosols

“…Brown et al [37] reported FMDV present within the cell cytoplasm of all epidermal skin layers in macroscopically normal epidermis. Other studies [45,46] have not observed the FMDV signal in the intact, non-lesional stratum corneum. There are no known studies of the infectivity of the stratum corneum in animal skin.…”

Analysis of a Foot-and-Mouth Disease Virus Type A 24 Isolate Containing an SGD Receptor Recognition Site In Vitro and Its Pathogenesis in Cattle

“…It is possible that the route of inoculation and the availability of appropriate integrin receptor molecules on the cells at the portal of entry may be the determining factor. Specifically, Breuss and coworkers (10) have reported that ␣ V ␤ 6 is expressed exclusively in epithelial cells, the cell type preferentially infected by FMDV in the susceptible host (2,(11)(12)(13), and ␣ V ␤ 6 appears to be the predominant integrin expressed in bovine tissues which also express viral antigen in infected animals (V. O'Donnell and B. Baxt, unpublished data). What is clear, however, is that once the SGD sequence has been established, there does not appear to be any selective pressure to change it to an RGD by infecting the animal either via IDL inoculation or direct contact.…”

Early Adaptive Immune Responses in the Respiratory Tract of Foot-and-Mouth Disease Virus-Infected Cattle

“…The rest of the animals were aerosol inoculated and then euthanized and necropsied at different time points from 2 to 6 days postinfection (dpi), except for two steers that were kept until 14 dpi and were sampled daily only for serum. Tissue collection was based on previous reports showing the main sites of FMDV replication along the respiratory tract (11,23,24). Samples obtained postmortem included 6 anatomically distinct organs and tissues: mandibular lymph nodes (ML), medial and lateral retropharyngeal lymph nodes (MRL and LRL, respectively), pharyngeal tonsils (PhT), tracheobronchial lymph nodes (TBL), and the spleen.…”