Distinct roles of enhancer nuclear factor 1 (NF1) sites in plasmacytoma and osteopetrosis induction by Akv1-99 murine leukemia virus
- Department of Molecular Biology, University of Aarhus, C.F. Mollers Alle, Building 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)
- Department of Molecular Biology, University of Aarhus, C.F. Mollers Alle, Building 130, DK-8000 Aarhus C (Denmark) and Department of Medical Microbiology and Immunology, University of Aarhus (Denmark)
Murine leukemia viruses (MLVs) can be lymphomagenic and bone pathogenic. In this work, the possible roles of two distinct proviral enhancer nuclear factor 1 (NF1) binding sites in osteopetrosis and tumor induction by B-lymphomagenic Akv1-99 MLV were investigated. Akv1-99 and mutants either with NF1 site 1, NF1 site 2 or both sites disrupted induced tumors (plasma cell proliferations by histopathology) with remarkably similar incidence and mean latency in inbred NMRI mice. Clonal immunoglobulin gene rearrangement detection, by Southern analysis, confirmed approximately half of the tumors induced by each virus to be plasmacytomas while the remaining lacked detectable clonally rearranged Ig genes and were considered polyclonal; a demonstration that enhancer NF1 sites are dispensable for plasmacytoma induction by Akv1-99. In contrast, X-ray analysis revealed significant differences in osteopetrosis induction by the four viruses strongly indicating that NF1 site 2 is critical for viral bone pathogenicity, whereas NF1 site 1 is neutral or moderately inhibitory. In conclusion, enhancer NF1 sites are major determinants of osteopetrosis induction by Akv1-99 without significant influence on viral oncogenicity.
- OSTI ID:
- 20726015
- Journal Information:
- Virology, Vol. 334, Issue 2; Other Information: DOI: 10.1016/j.virol.2005.01.039; PII: S0042-6822(05)00088-7; Copyright (c) 2005 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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