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
Services
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 Polony, T. S.
Right arrow Articles by Beemon, K. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Polony, T. S.
Right arrow Articles by Beemon, K. L.

 Previous Article  |  Next Article 

Journal of Virology, September 2003, p. 9378-9387, Vol. 77, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.17.9378-9387.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Silent Point Mutation in an Avian Retrovirus RNA Processing Element Promotes c-myb-Associated Short-Latency Lymphomas

Tatjana S. Polony,1 Sandra J. Bowers,2 Paul E. Neiman,2 and Karen L. Beemon1*

Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218,1 Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 981092

Received 3 March 2003/ Accepted 6 June 2003

The avian leukosis virus {Delta}LR-9 causes a high frequency of B-cell lymphomas within weeks after injection into 10-day-old chicken embryos. These lymphomas result from proviral integrations into the oncogene c-myb. In contrast, LR-9, which lacks the 42-nucleotide gag gene deletion of {Delta}LR-9, does not cause a high frequency of c-myb-associated short-latency lymphomas. Although viral replication rates and spliced env mRNA levels were found to be similar for both viruses, {Delta}LR-9 exhibited an increase in readthrough transcription compared to LR-9. The {Delta}LR-9 deletion is located in the region of the gag gene corresponding to the matrix (MA) protein as well as in the negative regulator of splicing (NRS) element. To test whether disruption of the NRS or of the MA protein was responsible for inducing short-latency lymphomas, we generated viruses with NRS point mutations that maintained the wild-type Gag amino acid sequence. One of the mutant viruses induced an even higher incidence than {Delta}LR-9 of short-latency lymphomas with viral integrations into c-myb. Thus, we propose that disruption of the NRS sequence promotes readthrough transcription and splicing to the downstream myb gene, causing overexpression of a slightly truncated Myb protein, which induces short-latency tumors.

* Corresponding author. Mailing address: Biology Department, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218. Phone: (410) 516-7289. Fax: (410) 516-7292. E-mail: KLB{at}jhu.edu.

Journal of Virology, September 2003, p. 9378-9387, Vol. 77, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.17.9378-9387.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bolisetty, M. T., Dy, G., Tam, W., Beemon, K. L. (2009). Reticuloendotheliosis Virus Strain T Induces miR-155, Which Targets JARID2 and Promotes Cell Survival. J. Virol. 83: 12009-12017 [Abstract] [Full Text]  
  • Yang, F., Xian, R. R., Li, Y., Polony, T. S., Beemon, K. L. (2007). Telomerase reverse transcriptase expression elevated by avian leukosis virus integration in B cell lymphomas. Proc. Natl. Acad. Sci. USA 104: 18952-18957 [Abstract] [Full Text]  
  • Wilusz, J. E., Beemon, K. L. (2006). The Negative Regulator of Splicing Element of Rous Sarcoma Virus Promotes Polyadenylation. J. Virol. 80: 9634-9640 [Abstract] [Full Text]  
  • Gorlov, I. P., Kimmel, M., Amos, C. I. (2006). Strength of the purifying selection against different categories of the point mutations in the coding regions of the human genome. Hum Mol Genet 15: 1143-1150 [Abstract] [Full Text]  
  • McNally, L. M., Yee, L., McNally, M. T. (2004). Two Regions Promote U11 Small Nuclear Ribonucleoprotein Particle Binding to a Retroviral Splicing Inhibitor Element (Negative Regulator of Splicing). J. Biol. Chem. 279: 38201-38208 [Abstract] [Full Text]  
  • GILES, K. E., CAPUTI, M., BEEMON, K. L. (2004). Packaging and reverse transcription of snRNAs by retroviruses may generate pseudogenes. RNA 10: 299-307 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»