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Previous Volume 338:1413-1421 May 14, 1998 Number 20 Next

	Full Text PDF Editorial by Rickinson, A.B. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Epstein–Barr virus (EBV) is associated with various malignant and benign lymphoproliferative disorders. It also efficiently transforms human B lymphocytes in vitro. The latent membrane protein 1 (LMP1) of EBV-infected cells plays a central part in this process by mimicking members of the family of tumor necrosis factor (TNF) receptors, thereby transmitting growth signals from the cell membrane to the nucleus through cytoplasmic TNF-receptor–associated factors (TRAFs). I sought evidence of LMP1-mediated signal transduction through TRAFs in tumor tissue from patients with post-transplantation lymphoproliferative disease and non-Hodgkin's lymphomas related to the acquired immunodeficiency syndrome (AIDS).

Methods The association of LMP1 with TRAF-1 or TRAF-3 in tumor tissue was studied with double-immunofluorescence microscopy and immunoprecipitation assays. Evidence of LMP1–TRAF signaling was sought with an electrophoretic mobility shift assay for the nuclear factor-B (NF-B) transcription factor.

Results Tumors from eight patients with post-transplantation lymphoproliferative disease, two patients with AIDS-associated non-Hodgkin's lymphoma, and three patients with endemic Burkitt's lymphoma were analyzed. Tumors from six of the patients with post-transplantation lymphoproliferative disease were positive for EBV and expressed LMP1; two samples were EBV-negative. Tumors from both patients with AIDS-associated non-Hodgkin's lymphoma were EBV-positive and expressed LMP1, whereas tumors from all three patients with Burkitt's tumors were positive for EBV but negative for LMP1. Double-immunofluorescence microscopy showed that LMP1 localized with and immunoprecipitated with TRAF-1 and TRAF-3 in all eight of the EBV-positive, LMP1-positive samples. An electrophoretic mobility shift assay revealed activated NF-B in all eight EBV-positive, LMP1-positive samples as well, but not in either of the EBV-negative, LMP1-negative samples or in the three EBV-positive, LMP1-negative samples.

Conclusions LMP1-mediated signaling through the TRAF system has a role in the pathogenesis of the EBV-positive lymphomas that arise in immunosuppressed patients.

Source Information

From the Marjorie B. Kovler Viral Oncology Laboratories, Department of Medicine, Section of Hematology/Oncology and Virology, University of Chicago, Chicago. Presented in part at the National AIDS Malignancy Conference, Bethesda, Md., April 22, 1997.

Address reprint requests to Dr. Liebowitz at the University of Chicago Medical Center, Department of Medicine, Section of Hematology/Oncology, 5841 S. Maryland Ave., MC2115, Chicago, IL 60637.

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