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.
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.
DeMartini
J C
JC
Department of Pathology, Colorado State University, Fort Collins 80524, USA. jcdemar@cvmbs.colostate.edu
Bishop
J V
JV
Allen
T E
TE
Jassim
F A
FA
Sharp
J M
JM
de las Heras
M
M
Voelker
D R
DR
Carlson
J O
JO
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002461:Cell Line, Transformed; D004279:DNA, Viral; D006801:Humans; D022141:Jaagsiekte sheep retrovirus / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D008175:Lung Neoplasms; D008969:Molecular Sequence Data; D011510:Proteolipids / Q000235:genetics*; D011533:Proviruses / Q000235:genetics* / Q000302:isolation & purification; D011648:Pulmonary Adenomatosis, Ovine / Q000821:virology*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics*; D012756:Sheep; D014407:Tumor Cells, Cultured; D016662:Virus Integration / Q000235:genetics*
D004279:DNA, Viral; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants