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Journal of Virology, May 2001, p. 4239-4246, Vol. 75, No. 9
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.9.4239-4246.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Jaagsiekte Sheep Retrovirus Proviral Clone JSRVJS7, Derived from the JS7 Lung Tumor Cell Line, Induces Ovine Pulmonary Carcinoma and Is Integrated into the Surfactant Protein A Gene

James C. DeMartini,1,* Jeanette V. Bishop,1 Thomas E. Allen,1 F. A. Jassim,2 J. Michael Sharp,2 Marcelo de las Heras,3 Dennis R. Voelker,4 and Jonathan O. Carlson5

Departments of Pathology1 and Microbiology,5 Colorado State University, Fort Collins, and National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver,4 Colorado; the Moredun Research Institute, International Research Center, Penicuik, Midlothian, United Kingdom2; and Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, Spain3

Received 8 December 2000/Accepted 6 February 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 (JSRVJS7) 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 JSRVJS7 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.

* Corresponding author. Mailing address: Department of Pathology, Colorado State University, Fort Collins, CO 80524. Phone: (970) 491-5410. Fax: (970) 491-0603. E-mail: jcdemar{at}cvmbs.colostate.edu.

Journal of Virology, May 2001, p. 4239-4246, Vol. 75, No. 9
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.9.4239-4246.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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