HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Snow, A. L. Articles by Martinez, O. M. Search for Related Content PubMed PubMed Citation Articles by Snow, A. L. Articles by Martinez, O. M.

EBV Can Protect Latently Infected B Cell Lymphomas from Death Receptor-Induced Apoptosis¹

Andrew L. Snow^2,*,, Stacie L. Lambert^*,, Yasodha Natkunam, Carlos O. Esquivel, Sheri M. Krams^*, and Olivia M. Martinez^3,*,

^* Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305; Department of Surgery/Division of Transplantation, Stanford University School of Medicine, Stanford, CA 94305; and Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305

The relationship between EBV infection and sensitivity to death receptor (DR)-induced apoptosis is poorly understood. Using EBV^– and EBV⁺ BJAB cells, we provide the first evidence that EBV can protect latently infected B cell lymphomas from apoptosis triggered through Fas or TRAIL receptors. Caspase 8 activation was impaired and cellular FLIP recruitment was enriched in death-inducing signaling complexes formed in EBV-infected BJAB cells relative to parent BJAB cells. Furthermore, latent membrane protein 1 expression alone could reduce caspase activation and confer partial resistance to DR apoptosis in BJAB cells. This protective effect was dependent on C-terminal activating region 2-driven NF-B activation, which in turn up-regulated cellular FLIP expression in latent membrane protein 1⁺ BJAB cells. Thus, the ability of latent EBV to block DR apoptosis may help to ensure the survival of host cells during B cell differentiation, and contribute to the development of B cell lymphomas, especially in immunocompromised individuals.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants RO1 AI41769 and CA105157 (to O.M.M.) and a Roche Organ Transplantation Research Foundation award (to O.M.M.). A.L.S. was supported by a Howard Hughes Medical Institute predoctoral fellowship. S.L.L. was supported by an American Cancer Society postdoctoral fellowship.

² Current address: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, 11N311, 10 Center Drive, MSC 1892, Bethesda, MD 20892.

³ Address correspondence and reprint requests to Dr. Olivia M. Martinez, MSLS P312, 1201 Welch Road, Stanford, CA 94305-5492. E-mail address: omm{at}stanford.edu

⁴ Abbreviations used in this paper: PTLD, posttransplant lymphoproliferative disease; LMP, latent membrane protein; BL, Burkitt’s lymphoma; cFLIP, cellular FLIP; cFLIP_L, long isoform of cFLIP; cFLIP_S, short isoform of cFLIP; CTAR, C-terminal activating region; DISC, death-inducing signaling complex; DR, death receptor; EBNA, EBV nuclear Ag; EGFP, enhanced GFP; FADD, Fas-associated death domain protein; FasL, Fas ligand; IP, immunoprecipitation; NGFR, nerve growth factor receptor; PI, propidium iodide; TRAF, TNFR-associated factor; WB, Western blot; WT, wild type.

This article has been cited by other articles:

				S. L. Lambert and O. M. Martinez Latent Membrane Protein 1 of EBV Activates Phosphatidylinositol 3-Kinase to Induce Production of IL-10 J. Immunol., December 15, 2007; 179(12): 8225 - 8234. [Abstract] [Full Text] [PDF]