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Journal of Virology, January 2003, p. 105-114, Vol. 77, No. 1
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.1.105-114.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Epstein-Barr Virus LMP2A Interferes with Global Transcription Factor Regulation When Expressed during B-Lymphocyte Development

Toni Portis and Richard Longnecker*

Department of Microbiology and Immunology, Northwestern University, Chicago, Illinois 60611

Received 19 July 2002/ Accepted 26 September 2002

Epstein-Barr virus (EBV) is associated with the development of malignant lymphomas and lymphoproliferative disorders in immunocompromised individuals. The LMP2A protein of EBV is thought to play a central role in this process by allowing the virus to persist in latently infected B lymphocytes. We have demonstrated that LMP2A, when expressed in B cells of transgenic mice, allows normal B-cell developmental checkpoints to be bypassed. To identify cellular genes targeted by LMP2A that are involved in this process, we have utilized DNA microarrays to compare gene transcription in B cells from wild-type versus LMP2A transgenic mice. In B cells from LMP2A transgenic mice, we observed decreased expression of many genes associated with normal B-cell development as well as reduced levels of the transcription factors that regulate their expression. In particular, expression of the transcription factor E2A was down-regulated in bone marrow and splenic B cells. Furthermore, E2A activity was inhibited in these cells as determined by decreased DNA binding and reduced expression of its target genes, including the transcription factors early B-cell factor and Pax-5. Expression of two E2A inhibitors, Id2 and SCL, was up-regulated in splenic B cells expressing LMP2A, suggesting a possible mechanism for E2A inhibition. These results indicate that LMP2A deregulates transcription factor expression and activity in developing B cells, and this likely allows for a bypass of normal signaling events required for proper B-cell development. The ability of LMP2A to interfere with B-cell transcription factor regulation has important implications regarding its role in EBV latency.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Northwestern University, Ward 6-231, 303 E. Chicago Ave., Chicago, IL 60611. Phone: (312) 503-0467. Fax: (312) 503-1339. E-mail: r-longnecker{at}nwu.edu.

Journal of Virology, January 2003, p. 105-114, Vol. 77, No. 1
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.1.105-114.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Stewart, S., Dawson, C. W., Takada, K., Curnow, J., Moody, C. A., Sixbey, J. W., Young, L. S. (2004). Epstein-Barr virus-encoded LMP2A regulates viral and cellular gene expression by modulation of the NF-{kappa}B transcription factor pathway. Proc. Natl. Acad. Sci. USA 101: 15730-15735 [Abstract] [Full Text]  


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