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Journal of Virology, May 2005, p. 5499-5506, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5499-5506.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Modulation of the Cell Growth Regulator mTOR by Epstein-Barr Virus-Encoded LMP2A

Cary A. Moody,1,2 Rona S. Scott,1,2,4 Nazanin Amirghahari,3 Cherie-Ann Nathan,3,4 Lawrence S. Young,5 Chris W. Dawson,5 and John W. Sixbey1,2,4*

Center for Molecular and Tumor Virology,1 Department of Microbiology and Immunology,2 Department of Otolaryngology and Head and Neck Surgery,3 Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130,4 Cancer Research United Kingdom Institute for Cancer Studies, Birmingham B15-2TT, United Kingdom5

Received 3 May 2004/ Accepted 20 December 2004

Control of translation initiation is one means by which cells regulate growth and proliferation, with components of the protein-synthesizing machinery having oncogenic potential. Expression of latency protein LMP2A by the human tumor virus Epstein-Barr virus (EBV) activates phosphatidylinositol 3-kinase/Akt located upstream of an essential mediator of growth signals, mTOR (mammalian target of rapamycin). We show that mTOR is activated by expression of LMP2A in carcinoma cells, leading to wortmannin- and rapamycin-sensitive inhibition of the negative regulator of translation, eukaryotic initiation factor 4E-binding protein 1, and increased c-Myc protein translation. Intervention by this DNA tumor virus in cellular translational controls is likely to be an integral component of EBV tumorigenesis.

* Corresponding author. Mailing address: Microbiology and Immunology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130. Phone: (318) 675-4272. Fax: (318) 675-5764. E-mail: jsixbe{at}lsuhsc.edu.

Journal of Virology, May 2005, p. 5499-5506, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5499-5506.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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