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Journal of Virology, August 2006, p. 8038-8046, Vol. 80, No. 16
0022-538X/06/$08.00+0     doi:10.1128/JVI.00180-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Oncogenic Activity of Epstein-Barr Virus Latent Membrane Protein 1 (LMP-1) Is Down-Regulated by Lytic LMP-1

Jyotsna Pandya1 and Dennis M. Walling1,2*

Division of Infectious Diseases, Department of Internal Medicine,1 Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, Texas 77555-04352

Received 26 January 2006/ Accepted 22 May 2006

The Epstein-Barr virus (EBV) is an oncogenic human herpesvirus. EBV latent membrane protein 1 (LMP-1) is a viral oncogene that manifests its oncogenic phenotype through activation of cellular signaling pathways involved in cell growth, survival, differentiation, and transformation. Lytic LMP-1 (lyLMP-1) is a related EBV gene without oncogenic properties. The lyLMP-1 gene is found in 60% of the EBV strains circulating in nature, but it is not found in EBV strains associated with nasopharyngeal carcinoma. We recently demonstrated that lyLMP-1 down-regulates the half-life of LMP-1 in epithelial cells. Therefore in this study, we tested the hypothesis that lyLMP-1 concomitantly down-regulates LMP-1 oncogenic activity. The results demonstrated that lyLMP-1 inhibits LMP-1-mediated intracellular signaling activation, epithelial cell growth and survival, and fibroblast cell transformation in a dose-dependent manner. Lytic LMP-1 manifested this effect through the promotion of LMP-1 degradation and a reduction in the expressed quantity of LMP-1. Thus, lyLMP-1 functions as a posttranslational negative regulator of LMP-1 oncogenesis. These results support a model of EBV-associated epithelial oncogenesis in which lyLMP-1 may act in vivo to reduce the risk of LMP-1-mediated transformation and is therefore subjected to negative selection in nasopharyngeal carcinoma pathogenesis.

* Corresponding author. Mailing address: Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555-0435. Phone: (409) 747-0236. Fax: (409) 772-6527. E-mail: dwalling{at}utmb.edu.

Journal of Virology, August 2006, p. 8038-8046, Vol. 80, No. 16
0022-538X/06/$08.00+0     doi:10.1128/JVI.00180-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lo, A. K. F., To, K. F., Lo, K. W., Lung, R. W. M., Hui, J. W. Y., Liao, G., Hayward, S. D. (2007). Modulation of LMP1 protein expression by EBV-encoded microRNAs. Proc. Natl. Acad. Sci. USA 104: 16164-16169 [Abstract] [Full Text]  


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