Host species barriers to Jaagsiekte sheep retrovirus replication and carcinogenesis.

Understanding the factors governing host species barriers to virus transmission has added significantly to our appreciation of virus pathogenesis. Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA), a transmissible lung cancer of sheep that has rarely been found in goats. In this study, in order to further clarify the pathogenesis of OPA, we investigated whether goats are resistant to JSRV replication and carcinogenesis. We found that JSRV induces lung tumors in goats with macroscopic and histopathological features that dramatically differ from those in sheep. However, the origins of the tumor cells in the two species are identical. Interestingly, in experimentally infected lambs and goat kids, we revealed major differences in the number of virus-infected cells at early stages of infection. These differences were not related to the number of available target cells for virus infection and cell transformation or the presence of a host-specific immune response toward JSRV. Indeed, we also found that goats possess transcriptionally active endogenous retroviruses (enJSRVs) that likely influence the host immune response toward the exogenous JSRV. Overall, these results suggest that goat cells, or at least those cells targeted for viral carcinogenesis, are not permissive to virus replication but can be transformed by JSRV.

[Enzootic nasal adenocarcinoma in a dairy sheep flock]. / Enzootische nasale Adenokarzinome in einem Milchschafbestand.

In a herd of dairy sheep several losses occurred due to a respiratory syndrome in combination with progressive wasting. Clinical and pathomorphological diagnostics of 3 sheep revealed the presence of cancerous masses in the nasal cavities. These neoplasms were identified as adenocarcinomas originating from the nasal mucosa. Etiologically, they were attributed to JRSV (Jaagsiekte Sheep Retrovirus) by detection of capsid protein 24 in western blot. The significance of the disease in Switzerland is discussed, also in the context of lung adenomatosis.

Infection of lung epithelial cells and induction of pulmonary adenocarcinoma is not the most common outcome of naturally occurring JSRV infection during the commercial lifespan of sheep.

Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA). In this study, we followed over a 31-month period the natural transmission of JSRV in adult sheep and in their offspring. We established groups derived from flocks with either a high or low incidence of OPA and monitored virus transmission, clinical disease and macroscopic/microscopic lung lesions at necropsy. Results obtained show that (i) JSRV infection can occur perinatally or in the first few months of life in lambs and in adult sheep; (ii) only a minority of JSRV-infected animals develop clinical disease during their commercial lifespan; and (iii) JSRV is more readily detectable in peripheral blood leucocytes and lymphoid organs than in the lungs. These data support a model of opportunistic JSRV infection and tumorigenic conversion of type II pneumocytes/Clara cells in the lungs, while lymphoreticular cells serve as the principal virus reservoir.

Pathological and epidemiological aspects of the coexistence of maedi-visna and sheep pulmonary adenomatosis.

Between 1982 and 1991, 159 sheep suffering from chronic respiratory disease were subjected to clinical, pathological, histopathological and serological examination. Maedi was diagnosed in 82 sheep and sheep pulmonary adenomatosis (SPA) in another 59. Forty-one of the latter (69.5 per cent) were seropositive for maedi-visna (MV) virus infection, but only six (10.2 per cent) showed concurrent lung lesions of maedi. Even disregarding the MV seronegative sheep and those younger than two years old, the rate of concurrent maedi lesions did not exceed 18 per cent. During a similar period, 5060 sheep from 161 flocks (86 of which also provided the 159 affected animals) were tested for antibodies to MV virus. The average seroprevalence of MV virus infection among flocks in which SPA was detected was 66.4 per cent, whereas in those in which SPA could not be demonstrated, and in those in which necropsies were not performed, the levels of MV virus infection were 55.1 per cent and 43.6 per cent, respectively. The effect of SPA on the seroprevalence of MV virus infection was independent of other factors, such as breed of sheep or the size of the flocks. These results provide evidence that SPA plays a role in the spread of MV virus infection, although a synergistic effect of the simultaneous infection on the expression of concurrent lesions does not seem to occur.

[Double infection with maedi virus and adenomatosis virus in Merino sheep]. / Doppelinfektion mit Maedi-Virus und Adenomatose-Virus bei Merinolandschafen.

This is the first report of the simultaneous occurrence of sheep pulmonary adenomatosis and lymphoid interstitial pneumonia (Maedi) in the same animal in the Federal Republic of Germany. Seven adult sheep of the Merino Landrace were tested by immunodiffusion-assay for antibodies against Maedi/Visna-virus. Five of them originating from three different flocks had a positive reaction. In all pulmonary foci, which were examined by light microscopy, we found proliferations of the alveolar epithelium and therefore made a diagnosis of pulmonary adenomatosis. The animals with antibodies against Maedi-virus were additionally affected by a non-purulent peribronchitis and interstitial pneumonia. The diagnostic difficulties in double infections like those reported here are discussed. Eradication is complicated by the unknown epidemiologic situation.

Maedi-visna and sheep pulmonary adenomatosis: a study of concurrent infection.

The transmission of maedi-visna (MV) virus was studied within two groups of sheep, one of which was also affected with sheep pulmonary adenomatosis (SPA). Serological monitoring of sheep kept in contact with both groups indicated that MV virus replication occurred to a greater extent in the group with both diseases, three of five in-contact sheep being seropositive after 1 year's exposure compared with none of six held with MV-virus-only infected lambs.

Concurrent maedi-visna virus infection and pulmonary adenomatosis in a commercial breeding flock in East Anglia.

The seroprevalence of maedi-visna virus infection in thin potential cull ewes aged over two years in a flock in East Anglia increased from 3.7 per cent in August 1985 to 39.0 per cent in September 1987 and 93.3 per cent in May 1989. This increase coincided with the first appearance of sheep pulmonary adenomatosis in the flock. Four emaciated ewes which were dyspnoeic were necropsied between 1987 and 1989. Maedi and pulmonary adenomatosis were confirmed histologically in one of these ewes and pulmonary adenomatosis was confirmed in the other three.

Lesions and retroviruses associated with naturally occurring ovine pulmonary carcinoma (sheep pulmonary adenomatosis).

Five sheep with ovine pulmonary carcinoma were markedly dyspneic and had sporadic coughing; two had copious watery nasal exudate. In four, lesions consisted of multifocal nodules of neoplastic cuboidal epithelial cells in acinar or papillary patterns. Electron microscopically, cells had microvilli, tight junctions, and cytoplasmic lamellar bodies typical of alveolar type II cells. One sheep had a single lung tumor of nonciliated bronchiolar epithelial cells. Vacuolated alveolar macrophages surrounded adenomatous foci. One sheep had a metastatic lesion in the caudal mediastinal lymph node. All sheep had histologic lesions of lymphoid interstitial pneumonia (LIP, ovine progressive pneumonia) consisting of peribronchiolar and interstitial lymphoid hyperplasia, and fibromuscular proliferation; all had serum precipitating antibodies to ovine lentivirus. Lung fluids or tumor homogenates contained a 26-kd peptide that crossreacted with a primate-derived type D retrovirus as detected by immunoblotting or interspecies competition radioimmunoassay. Ovine lentivirus was isolated from concentrated lung fluids or tumor tissues of four sheep tested and from tumor cell DNA of one animal transfected into ovine muscle cells. These studies document the presence of type D-related retrovirus antigen in ovine pulmonary carcinoma (OPC) in the United States and indicate that lentivirus-induced LIP is a lesion frequently associated with this disease.