Sheep pulmonary adenomatosis (SPA) is a naturally occurring contagious lung tumour of sheep which has been associated aetiologically with a type D-and Brelated retrovirus (Jaagsiekte retrovirus; JSRV). To improve understanding of the aetio-pathogenesis of SPA, the distribution and the sites of JSRV replication in sheep with naturally or experimentally induced SPA or in unaffected controls were identified. New immunological reagents were produced and a blocking enzymelinked immunosorbent assay (B-ELISA) and an immunohistochemical technique for the detection of JSRV major capsid protein at the tissue and cellular levels were developed. JSRV was detected only in the respiratory tract of sheep affected by pulmonary adenomatosis and specifically in the transformed epithelial cells of the alveoli of SPA-affected sheep.

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Ovine pulmonary adenocarcinoma (OPA) can be reproduced consistently in neonatal lambs by intratracheal injection of inocula containing jaagsiekte sheep retrovirus (JSRV). In this study, clinical disease, confirmed pathologically as OPA, was induced in a high proportion of lambs that had been inoculated intratracheally with infectious lung fluid at 1, 3 and 6 months of age. The incubation periods, however, were longer in these three age groups than in 1-week-old lambs that were used as controls. Viraemia was detected in all age groups before onset of clinical signs, but occurred later in older animals. These results suggest an age-dependent susceptibility to OPA that could be determined by the availability of JSRV target cells in the ovine lung. The feasibility of inducing OPA in older lambs and detecting JSRV viraemia in preclinical stages enables improved studies on the pathogenesis, assessment of vaccines, diagnosis and control of the disease.

Abstract. The successful experimental transmission of enzootic intranasal tumor (EIT) from goat to goat is described. Ten kids, less than 48 hours old, from a Hock free of the disease and seronegative for ruminant lentiviruses were inoculated intranasally or intrasinusally with either nasal Huid from goats with naturally occurring EIT or EIT retrovirus concentrated from such Huids. EIT was induced in three kids after 12-24 months. The EIT retrovirus was demonstrated in tumor material from each of the three kids by western blotting and electron microscopy. All kids were seronegative for ruminant lentiviruses.

Peripheral blood leukocytes (PBLs) and tissue samples from 36 sheep were examined for jaagsiekte sheep retrovirus (JSRV) by hemi-nested PCR. Animals were classified according to the status of sheep pulmonary adenomatosis (SPA), which was confirmed by pathological examination, as follows : (i) sheep with classical SPA (cSPA, n l 10), (ii) sheep with atypical SPA (aSPA, n l 6), (iii) nonaffected sheep from SPA-affected flocks (in-contact, n l 10) and (iv) non-affected sheep from SPA-free flocks (control, n l 10). JSRV proviral DNA was detected in the PBLs of 10/10 cSPA, 5/6 aSPA, 4/10 in-contact and 0/10 control sheep. Lung tumours and lymphoid organs were also found to be JSRV-positive. The number of positive PCR results was greater for sheep in the cSPA group than for those in the aSPA and in-contact groups. For the first time, it is concluded that JSRV can be detected in naturally infected sheep before the onset of clinical disease and even before the development of discernible tumours. Sheep pulmonary adenomatosis (SPA, also known as jaagsiekte) is a worldwide transmissible lung cancer of sheep that was shown recently to be caused by an exogenous type D retrovirus, jaagsiekte sheep retrovirus (JSRV ; Palmarini et al., 1999). To date, diagnosis has been possible only when clinical signs become apparent and not during the pre-clinical period of the disease. This is due to a lack of circulating JSRV-specific antibodies, as demonstrated by Western blotting (Sharp &