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 Geiger, T. R.
Right arrow Articles by Martin, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Geiger, T. R.
Right arrow Articles by Martin, J. M.

 Previous Article  |  Next Article 

Journal of Virology, December 2006, p. 11638-11650, Vol. 80, No. 23
0022-538X/06/$08.00+0     doi:10.1128/JVI.01570-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The Epstein-Barr Virus-Encoded LMP-1 Oncoprotein Negatively Affects Tyk2 Phosphorylation and Interferon Signaling in Human B Cells{triangledown}

Timothy R. Geiger{dagger} and Jennifer M. Martin*

Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado 80309

Received 21 July 2006/ Accepted 8 September 2006

Epstein-Barr virus (EBV) establishes a persistent infection in the human host and is associated with a variety of human cancers. Persistent infection results from a balance between the host immune response and viral immune evasion mechanisms. EBV infection is controlled initially by the innate immune response and later by T-cell-mediated adaptive immunity. EBV has evolved mechanisms to evade the host immune response so that it can persist for the lifetime of the host. Latent membrane protein 1 (LMP-1) is the EBV oncoprotein essential for B-cell immortalization by EBV. We show here that LMP-1 interacts with Tyk2, a signaling intermediate in the alpha interferon (IFN-{alpha}) signaling pathway, via a previously uncharacterized LMP-1 signaling domain. LMP-1 prevents Tyk2 phosphorylation and inhibits IFN-{alpha}-stimulated STAT2 nuclear translocation and interferon-stimulated response element transcriptional activity. Long-term culture of EBV+ lymphoblastoid cells in IFN-{alpha} is associated with outgrowth of a population expressing elevated LMP-1 protein levels, suggesting that cells expressing higher levels of LMP-1 survive the antiproliferative selective pressure imposed by IFN-{alpha}. These results show that LMP-1 can protect EBV+ cells from the IFN-{alpha}-stimulated antiviral/antiproliferative response and suggest that chronic IFN-{alpha} treatment may encourage the outgrowth of cells expressing elevated, and therefore potentially oncogenic, LMP-1 levels in EBV+ individuals.

* Corresponding author. Mailing address: Department of Molecular, Cellular and Developmental Biology, University of Colorado, Campus Box 347, Boulder, CO 80309. Phone: (303) 492-6346. Fax: (303) 492-1587. E-mail: jm{at}colorado.edu.

{triangledown} Published ahead of print on 20 September 2006.

{dagger} Present address: Department of Biochemistry, Colorado State University, Fort Collins, CO 80523.

Journal of Virology, December 2006, p. 11638-11650, Vol. 80, No. 23
0022-538X/06/$08.00+0     doi:10.1128/JVI.01570-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Martin, H. J., Lee, J. M., Walls, D., Hayward, S. D. (2007). Manipulation of the Toll-Like Receptor 7 Signaling Pathway by Epstein-Barr Virus. J. Virol. 81: 9748-9758 [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»