Jaagsiekte sheep retrovirus proviral clone JSRV(JS7), derived from the JS7 lung tumor cell line, induces ovine pulmonary carcinoma and is integrated into the surfactant protein A gene

• Published in: Journal of virology 2001-05, Vol.75 (9), p.4239-4246
• Main Authors: DeMartini, J C, Bishop, J V, Allen, T E, Jassim, F A, Sharp, J M, de las Heras, M, Voelker, D R, Carlson, J O
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Binding Sites; Cell Line, Transformed; DNA, Viral; Humans; Jaagsiekte sheep retrovirus - genetics; Jaagsiekte sheep retrovirus - isolation & purification; Jaagsiekte sheep retrovirus - pathogenicity; Lung Neoplasms; Molecular Sequence Data; Proteolipids - genetics; Proviruses - genetics; Proviruses - isolation & purification; Pulmonary Adenomatosis, Ovine - virology; Pulmonary Surfactant-Associated Protein A; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants - genetics; Sheep; Tumor Cells, Cultured; Virus Integration - genetics
• ISSN: 0022-538X
• DOI: 10.1128/JVI.75.9.4239-4246.2001

Ovine pulmonary carcinoma (OPC) is a contagious neoplasm of alveolar epithelial type II (ATII) or Clara cells caused by a type D/B chimeric retrovirus, jaagsiekte sheep retrovirus (JSRV). Here we report the isolation, sequencing, pathogenicity, and integration site of a JSRV provirus isolated from a sheep lung tumor cell line (JS7). The sequence of the virus was 93 to 99% identical to other JSRV isolates and contained all of the expected open reading frames. To produce virions and test its infectivity, the JS7 provirus (JSRV(JS7)) was cloned into a plasmid containing a cytomegalovirus promoter and transfected into 293T cells. After intratracheal inoculation with virions from concentrated supernatant fluid, JSRV-associated OPC lesions were found in one of four lambs, confirming that JSRV(JS7) is pathogenic. In JS7-cell DNA, the viral genome was inserted in the protein-coding region for the surfactant protein A (SP-A) gene, which is highly expressed in ATII cells, in an orientation opposite to the direction of transcription of the SP-A gene. No significant transcription was detected from either the viral or the SP-A gene promoter in the JS7 cell line at passage level 170. The oncogenic significance of the JSRV proviral insertion involving the SP-A locus in the JS7 tumor cell line is unknown.