Direct transformation of rodent fibroblasts by jaagsiekte sheep retrovirus DNA

Maeda, N., Palmarini, M. , Murgia, C. and Fan, H. (2001) Direct transformation of rodent fibroblasts by jaagsiekte sheep retrovirus DNA. Proceedings of the National Academy of Sciences of the United States of America, 98(8), pp. 4449-4454. (doi:10.1073/pnas.071547598)

Full text not currently available from Enlighten.

Publisher's URL: http://dx.doi.org/10.1073/pnas.071547598

Abstract

Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary carcinoma, a unique animal model for human bronchioalveolar carcinoma. We previously isolated a JSRV proviral clone and showed that it was both infectious and oncogenic. Thus JSRV is necessary and sufficient for the development of ovine pulmonary carcinoma, but no data are available on the mechanisms of transformation. Inspection of the JSRV genome reveals standard retroviral genes, but no evidence for a viral oncogene. However, an alternate ORF in pol (orf-x) might be a candidate for a transforming gene. We tested whether the JSRV genome might encode a transforming gene by transfecting an expression plasmid for JSRV [pCMVJS21, driven by the cytomegalovirus (CMV) immediate early promoter] into mouse NIH 3T3 cells. Foci of transformed cells appeared in the transfected cultures 2-3 weeks posttransfection; cloned transformants showed anchorage independence for growth, and they expressed JSRV RNA. These results indicate that the JRSV genome contains information with direct transforming potential for NIH 3T3 cells. Transfection of a mutated version of pCMVJS21 in which the orf-x protein was terminated by two stop codons also gave transformed foci. Thus, orf-x was eliminated as the candidate transforming gene. In addition, another derivative of pCMVJS21 (pCMVJS21GP) in which the gag, pol (and orf-x) coding sequences were deleted also gave transformed foci. These results indicate that the envelope gene carries the transforming potential. This is an unusual example of a native retroviral structural protein with transformation potential.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Palmarini, Professor Massimo and Murgia, Dr Claudio
Authors: Maeda, N., Palmarini, M., Murgia, C., and Fan, H.
Subjects:S Agriculture > SF Animal culture > SF600 Veterinary Medicine
Q Science > QR Microbiology > QR355 Virology
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
ISSN:0027-8424
ISSN (Online):1091-6490
Related URLs:

University Staff: Request a correction | Enlighten Editors: Update this record