Enhancer mutations of Akv murine leukemia virus inhibit the induction of mature B-cell lymphomas and shift disease specificity towards the more differentiated plasma cell stage
- Department of Molecular Biology, University of Aarhus, C.F. Mollers Alle, Bldg. 130, DK-8000 Aarhus C (Denmark)
- Institute of Pathology, GSF-National Research Center for Environment and Health, Neuherberg (Germany)
- Department of Comparative Medicine, GSF-National Research Center for Environment and Health, Neuherberg (Germany)
This study investigates the role of the proviral transcriptional enhancer for B-lymphoma induction by exogenous Akv murine leukemia virus. Infection of newborn inbred NMRI mice with Akv induced 35% plasma cell proliferations (PCPs) (consistent with plasmacytoma), 33% diffuse large B-cell lymphomas, 25% follicular B-cell lymphomas and few splenic marginal zone and small B-cell lymphomas. Deleting one copy of the 99-bp proviral enhancer sequence still allowed induction of multiple B-cell tumor types, although PCPs dominated (77%). Additional mutation of binding sites for the glucocorticoid receptor, Ets, Runx, or basic helix-loop-helix transcription factors in the proviral U3 region, however, shifted disease induction to almost exclusively PCPs, but had no major influence on tumor latency periods. Southern analysis of immunoglobulin rearrangements and ecotropic provirus integration patterns showed that many of the tumors/cell proliferations induced by each virus were polyclonal. Our results indicate that enhancer mutations weaken the ability of Akv to induce mature B-cell lymphomas prior to the plasma cell stage, whereas development of plasma cell proliferations is less dependent of viral enhancer strength.
- OSTI ID:
- 20977027
- Journal Information:
- Virology, Vol. 362, Issue 1; Other Information: DOI: 10.1016/j.virol.2006.12.016; PII: S0042-6822(06)00897-X; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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