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Journal of Virology, July 1999, p. 6117-6122, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Replication and Pathogenicity of Primer Binding Site Mutants of SL3-3 Murine Leukemia Viruses

Anders H. Lund,1 Jörg Schmidt,2 Arne Luz,3 Annette Balle Sørensen,1 Mogens Duch,1 and Finn Skou Pedersen1,4,*

Department of Molecular and Structural Biology1 and Department of Medical Microbiology and Immunology,4 University of Aarhus, DK-8000 Aarhus C, Denmark, and GSF Institute for Molecular Virology2 and GSF Institute for Pathology,3 Neuherberg, D-85764, Germany

Received 24 November 1998/Accepted 5 April 1999

Retroviral reverse transcription is primed by a cellular tRNA molecule annealed to an 18-bp primer binding site sequence. The sequence of the primer binding site coincides with that of a negatively acting cis element that mediates transcriptional silencing of murine leukemia virus (MLV) in undifferentiated embryonic cells. In this study we test whether SL3-3 MLV can replicate stably using tRNA primers other than the cognate tRNAPro and analyze the effect of altering the primer binding site sequence to match the 3' end of tRNA1Gln, tRNA3Lys, or tRNA1,2Arg in a mouse pathogenicity model. Contrary to findings from cell culture studies of primer binding site-modified human immunodeficiency virus type 1 and avian retroviruses, our findings were that SL3-3 MLV may stably and efficiently replicate with tRNA primers other than tRNAPro. Although lymphoma induction of the SL3-3 Lys3 mutant was significantly delayed relative to that of the wild-type virus, molecular tumor analysis indicated that all the primer binding site-modified viruses induce T-cell lymphomas similar to those induced by the wild-type virus in terms of frequencies of genomic rearrangements within the T-cell receptor beta -chain, the immunoglobulin kappa  light chain, and the c-myc locus. Whereas none of the mutants were found to revert to tRNAPro primer utilization, in two tumors resulting from the injection of the SL3-3 Lys3 mutant the primer binding site was altered to match that of a new primer species, tRNA1,2Lys. In addition, recombination with endogenous viruses resulting in the generation of recombinant viruses carrying a glutamine primer binding site was detected in the majority of the tumors induced by the SL3-3 Lys3 mutant as well as in two tumors induced by wild-type SL3-3 and the SL3-3 Arg1,2 mutant.

* Corresponding author. Mailing address: Department of Molecular and Structural Biology, University of Aarhus, C. F. Møllers Allé, Bldg. 130, DK-8000 Aarhus C, Denmark. Phone: 45 8942 3188. Fax: 45 8619 6500. E-mail: fsp{at}mbio.aau.dk.

Journal of Virology, July 1999, p. 6117-6122, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Nielsen, A. A., Sorensen, A. B., Schmidt, J., Pedersen, F. S. (2005). Analysis of Wild-Type and Mutant SL3-3 Murine Leukemia Virus Insertions in the c-myc Promoter during Lymphomagenesis Reveals Target Site Hot Spots, Virus-Dependent Patterns, and Frequent Error-Prone Gap Repair. J. Virol. 79: 67-78 [Abstract] [Full Text]  
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