This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Martiney, M. J.
Right arrow Articles by Lenz, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Martiney, M. J.
Right arrow Articles by Lenz, J.

 Previous Article  |  Next Article 

Journal of Virology, March 1999, p. 2143-2152, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Suppressor Mutations within the Core Binding Factor (CBF/AML1) Binding Site of a T-Cell Lymphomagenic Retrovirus

Marita J. Martiney,1 Laura S. Levy,2 and Jack Lenz1,*

Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York 10461,1 and Tulane University School of Medicine, New Orleans, Louisiana 701122

Received 20 August 1998/Accepted 2 December 1998

The transcriptional enhancer of the lymphomagenic mouse retrovirus SL3 contains a binding site for the transcription factor core binding factor (CBF; also called AML1, PEBP2, and SEF1). The SL3 CBF binding site is called the core. It differs from the core of the weakly lymphomagenic mouse retrovirus Akv by one nucleotide (the sequences are TGTGGTTAA and TGTGGTCAA, respectively). A mutant virus called SAA that was identical to SL3 except that its core was mutated to the Akv sequence was only moderately attenuated for lymphomagenicity. In most SAA-infected mice, tumor proviruses contained either reversions of the original mutation or one of two novel core sequences. In 20% of the SAA-infected mice, tumor proviruses retained the original SAA/Akv core mutation but acquired one of two additional mutations (underlined), TGCGGTCAA or TGTGGTCTA, that generated core elements called So and T*, respectively. We tested whether the novel base changes in the So and T* cores were suppressor mutations. SL3 mutants that contained So or T* cores in place of the wild-type sequence were generated. These viruses induced T-cell lymphomas in mice more quickly than SAA. Therefore, the mutations in the So and T* cores are indeed second-site suppressor mutations. The suppressor mutations increased CBF binding in vitro and transcriptional activity of the viral long terminal repeats (LTRs) in T lymphocytes to levels comparable to those of SL3. Thus, CBF binding was increased by any of three different nucleotide changes within the sequence of the SAA core. Increased CBF binding resulted in increased LTR transcriptional activity in T cells and in increased viral lymphomagenicity.

* Corresponding author. Mailing address: Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Phone: (718) 430-3715. Fax: (718) 430-8778. E-mail: lenz{at}aecom.yu.edu.

Journal of Virology, March 1999, p. 2143-2152, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Ejegod, D., Sorensen, K. D., Mossbrugger, I., Quintanilla-Martinez, L., Schmidt, J., Pedersen, F. S. (2009). Control of Pathogenicity and Disease Specificity of a T-Lymphomagenic Gammaretrovirus by E-Box Motifs but Not by an Overlapping Glucocorticoid Response Element. J. Virol. 83: 336-346 [Abstract] [Full Text]  
  • Johnson, C., Lobelle-Rich, P. A., Puetter, A., Levy, L. S. (2005). Substitution of Feline Leukemia Virus Long Terminal Repeat Sequences into Murine Leukemia Virus Alters the Pattern of Insertional Activation and Identifies New Common Insertion Sites. J. Virol. 79: 57-66 [Abstract] [Full Text]  
  • Sorensen, K. D., Quintanilla-Martinez, L., Kunder, S., Schmidt, J., Pedersen, F. S. (2004). Mutation of All Runx (AML1/Core) Sites in the Enhancer of T-Lymphomagenic SL3-3 Murine Leukemia Virus Unmasks a Significant Potential for Myeloid Leukemia Induction and Favors Enhancer Evolution toward Induction of Other Disease Patterns. J. Virol. 78: 13216-13231 [Abstract] [Full Text]  
  • Rulli, K., Lenz, J., Levy, L. S. (2002). Disruption of Hematopoiesis and Thymopoiesis in the Early Premalignant Stages of Infection with SL3-3 Murine Leukemia Virus. J. Virol. 76: 2363-2374 [Abstract] [Full Text]  
  • Martiney, M. J., Rulli, K., Beaty, R., Levy, L. S., Lenz, J. (1999). Selection of Reversions and Suppressors of a Mutation in the CBF Binding Site of a Lymphomagenic Retrovirus. J. Virol. 73: 7599-7606 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»