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Journal of Virology, April 2005, p. 5215-5219, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.5215-5219.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Induction of Apoptosis by Rewiring the Signal Transduction of Epstein-Barr Virus Oncoprotein LMP1 toward Caspase Activation

Eudoxia G. Hatzivassiliou, Theodore Tsichritzis, and George Mosialos*

Institute of Immunology, Biomedical Sciences Research Center Al. Fleming, Vari, Greece

Received 30 July 2004/ Accepted 23 November 2004

The Epstein-Barr virus latent membrane protein 1 (LMP1) is an oncoprotein which mimics activated tumor necrosis factor receptor family members. Here we demonstrate the principle that an inducible association of the LMP1 cytoplasmic carboxyl terminus with caspase-8 by a heterodimerizing agent causes apoptosis. This process depends on the catalytic activity of caspase-8 and the ability of LMP1 to oligomerize constitutively at the plasma membrane. Our data indicate that chemical inducers of the association of the LMP1 carboxyl terminus with caspase-8 can kill LMP1-expressing cells selectively. Such compounds could be used as chemotherapeutic agents for LMP1-associated malignancies.

* Corresponding author. Mailing address: Institute of Immunology, Biomedical Sciences Research Center Al. Fleming, 34 Al. Fleming St., Vari 16672, Greece, Phone: 30-2109656703. Fax: 30-2109653934. E-mail: mosialos{at}fleming.gr.

Journal of Virology, April 2005, p. 5215-5219, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.5215-5219.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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