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Journal of Virology, June 1999, p. 4662-4669, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Novel Endogenous Type D Retroviral Particles Expressed at High Levels in a SCID Mouse Thymic Lymphoma

Sika Ristevski,1,* Damian F. J. Purcell,2 John Marshall,3 Daniella Campagna,2 Sara Nouri,1 Simon P. Fenton,2,4 Dale A. McPhee,2 and George Kannourakis1,2,4,*

L.A.R.C.H. Cancer Research Unit, Royal Children's Hospital, Parkville, Victoria 3052,1 AIDS Cellular Biology Unit, Macfarlane Burnet Centre for Medical Research, Fairfield, Victoria 3078,2 Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria 3051,3 and Fiona Elsey Cancer Research Laboratory, Cancer Research Centre, University of Ballarat, St. John of God Hospital, Ballarat, Victoria 3350,4 Australia

Received 2 October 1998/Accepted 19 February 1999

A xenograft model of the human disease Langerhans cell histiocytosis (LCH) was investigated with severe combined immunodeficiency (SCID) mice. Transplantation of human LCH biopsy material into SCID mice resulted in the generation of mouse tumors resembling lymphomas. A thymoma cell line (ThyE1M6) was generated from one of these mice and found to display significant levels of Mg2+-dependent reverse transcriptase activity. Electron microscopy revealed particles with type D retroviral morphology budding from ThyE1M6 cells at a high frequency, whereas control cultures were negative. Reverse transcription-PCR of virion RNA with degenerate primers for conserved regions of various mouse, human, and primate retroviruses amplified novel sequences related to primate type D retroviruses, murine intracisternal A particles, Jaagsiekte sheep retrovirus, and murine long interspersed nuclear elements but not other retroviral classes. We demonstrate that these sequences represent a novel group of endogenous retroviruses expressed at low levels in mice but expressed at high levels in the ThyE1M6 cell line. Furthermore, we propose that the activation of endogenous retroviral elements may be associated with a high incidence of thymomas in SCID mice.

* Corresponding author. Present address for Sika Ristevski: Institute of Reproduction and Development, Monash Medical Centre, Clayton Rd., Clayton, Victoria 3168, Australia. Phone: 61-3-9594 7225. Fax: 61-3-9594 7211. E-mail: sika.ristevski{at}med.monash.edu.au. Mailing address for George Kannourakis: Fiona Elsey Cancer Research Laboratory, Cancer Research Centre, University of Ballarat, St. John of God Hospital, 1002 Mair St., Ballarat, Victoria 3350, Australia. Phone: 61-353-334 811. Fax: 61-353-334 813. E-mail: g.kannour{at}ballarat.edu.au.

Journal of Virology, June 1999, p. 4662-4669, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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