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Ovine pulmonary adenocarcinoma (OPA) and enzootic nasal adenocarcinoma (ENA) are two contagious neoplastic diseases of secretory epithelial cells in the respiratory system of sheep and goats. Jaagsiekte sheep retrovirus (JSRV) is the aetiological agent of OPA, and enzootic nasal tumour virus (ENTV) is associated with ENA. The genomes of these retroviruses do not contain known oncogenes but products of the env gene are important in the generation of transforming stimuli. However, the cell signalling pathways activated in vivo are not completely understood. This study was based on the use of activation stage antibodies specifically detecting proteins of the extracellular signal regulated kinase Erk 1/2 cell signalling pathway and transcription factors. Tissue sections were collected from four natural cases of OPA, four experimentally induced OPA tumours, four ENA tumours in sheep, four ENA tumours in goats, two normal sheep lungs and two lungs with chronic inflammation. Routine immunohistochemical procedures with phosphorylation stage-specific antibodies were carried out. Representative proteins of the Erk1/2 pathway (Raf-1, Mek1/2 and p44/42MAPK) were activated in natural cases of OPA and ENA in sheep and goats and also in experimentally induced OPA. Transcription factors 90Rsk and Elk-1 were activated in OPA and ENA tumours. However, c-Myc was activated only in OPA tumours. In contagious respiratory neoplasms of sheep and goats the Erk1/2 pathway appears to be important for the in-vivo generation of the transforming stimuli.

Ten sheep naturally affected with enzootic nasal adenocarcinoma (ENA), a disease associated with ovine enzootic nasal tumour virus (ENTV-1), were found also to be infected with jaagsiekte sheep retrovirus (JSRV), the causal agent of ovine pulmonary adenocarcinoma (OPA). Only one of the sheep showed OPA lung lesions. The animals belonged to 10 flocks located in a geographical area in which OPA is frequently seen. ENTV-1 was found in all the ENA tumours but only occasionally in extra-tumoral sites, confirming the results of a previous study. In contrast, JSRV had a disseminated tissue distribution, similar to that previously reported for animals infected with JSRV. However, the occurrence of JSRV in lymphoid tissues was clearly greater than in sheep infected with JSRV but with no lesions of ENA. The data suggested a synergistic relationship between ENTV-1 and JSRV, resulting in increased proliferation of JSRV.

Bronchiolo-alveolar carcinoma has been described in man and in several animal species, including cattle, dogs, opossums, goats and sheep. In sheep, a bronchiolo-alveolar carcinoma, known as ovine pulmonary carcinoma (OPC), is caused by jaagsiekte sheep retrovirus (JSRV), an exogenous type D retrovirus. In the mid-1980s, a severe outbreak of a disease resembling OPC was described in captive Sardinian moufflon (Ovis musimon). In the present study, the use of polymerase chain reaction (PCR) amplification of nucleic acids extracted from archival material established that JSRV was associated with OPC in affected moufflon. JSRV was detected in the lungs and mediastinal lymph nodes. Immunohistochemical and in-situ PCR demonstrated that in the lungs, JSRV proviral DNA was localized in transformed and untransformed type II pneumocytes and in the alveolar macrophages. In the mediastinal lymph nodes, JSRV DNA was mainly located in the cortical follicles and paracortex. These data suggest that JSRV is the cause of OPC in Sardinian moufflon, as it is in Sardinian sheep., (Copyright Harcourt Publishers Ltd.)

Natural paratuberculosis infection of rabbits (Oryctolagus cuniculus) was recently diagnosed in Scotland, and an investigation into the pathology of the disease in wild rabbits is reported in this paper. Evidence of Mycobacterium avium subsp. paratuberculosis (M.a. paratuberculosis) infection was detected in 22% of 110 rabbits; the organism was cultured from 17 of 110 rabbits, and histopathological lesions consistent with M.a. paratuberculosis infection were noted in 18 of 98 rabbits examined. No macroscopical lesions suggestive of M.a. paratuberculosis infection were observed. The histopathological lesions were either severe or mild. Severe lesions consisted of extensive macrophage granulomata and numerous giant cells, with many intracellular acid-fast bacteria in the small intestine. For the examination of formalin-fixed, paraffin wax-embedded tissues, neither immunohistochemistry nor the polymerase chain reaction was as sensitive a method of diagnosis as histopathology.

Pathological and immunohistochemical studies were performed on the lungs of 10 sheep with lesions of "classical" sheep pulmonary adenomatosis (SPA) and six sheep with "atypical" lung tumours. Lung tumour samples and other tissues from the same 16 animals were tested for the presence of jaagsiekte retrovirus (JSRV) by a polymerase chain reaction (PCR) that amplified a portion of the U3 long terminal repeat. The differences in the gross appearance of the classical and atypical forms paralleled the histopathological differences. The latter mainly concerned the stroma of the tumours which in the atypical cases was more heavily infiltrated by inflammatory cells and connective tissue fibres. JSRV major capsid protein was detected immunohistochemically in the epithelial transformed cells of both classical and atypical tumours, but the immune reactivity was slightly milder in atypical SPA. Proviral U3 sequences of JSRV were detected by specific PCR in all the tumour samples. Furthermore, the sequences of amplimers obtained from the two different pathological forms of the tumour were very similar. However, the dissemination of JSRV to other organs was greater in sheep with classical SPA than in those with atypical SPA. The pathological and virological features of these two forms of tumour are compared in an attempt to clarify whether classical and atypical SPA are two separate diseases or different expressions of a single disease spectrum., (Copyright 2000 Harcourt Publishers Ltd.)