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.

Abstract

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.

• Authors: J C DeMartini, J V Bishop, T E Allen, F A Jassim, J M Sharp, M de las Heras, D R Voelker, J O Carlson
• Journal: Journal of virology (J Virol) Vol. 75 Issue 9 Pg. 4239-46 (May 2001) ISSN: 0022-538X [Print] United States
• PMID: 11287573 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA, Viral
• Proteolipids
• Pulmonary Surfactant-Associated Protein A
• Pulmonary Surfactant-Associated Proteins
• Pulmonary Surfactants

Topics

• Animals
• Base Sequence
• Binding Sites
• Cell Line, Transformed
• DNA, Viral
• Humans
• Jaagsiekte sheep retrovirus (genetics, isolation & purification, pathogenicity)
• Lung Neoplasms
• Molecular Sequence Data
• Proteolipids (genetics)
• Proviruses (genetics, 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)