Jaagsiekte sheep retrovirus proviral clone JSRV(JS7), derived from the JS7lung tumor cell line, induces ovine pulmonary carcinoma and is integrated into the surfactant protein a gene

Ovine pulmonary carcinoma (OPC) is a contagious neoplasm of alveolar epithe lial type II (ATII) or Clara cells caused by a type DIB chimeric retrovirus , jaagsiekte sheep retrovirus (JSRV), Here we report the isolation, sequenc ing, 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 rea ding 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 viri ons from concentrated supernatant fluid, JSRV-associated OPC lesions were f ound 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 th e 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 th e SP-A gene promoter in the JS7 cell line at passage level 170, The oncogen ic significance of the JSRV proviral insertion involving the SP-A locus in the JS7 tumor cell line is unknown.