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PMID: 9751773 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Expression of the Epstein-Barr virus latent membrane protein 1 induces B cell lymphoma in transgenic mice.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 20 ·1998-09-29 ·Pages 11963-8

Kulwichit W, Edwards RH, Davenport EM, Baskar JF, Godfrey V, Raab-Traub N

Abstract

The latent membrane protein 1 (LMP1) of the Epstein-Barr virus has transforming properties in rodent fibroblasts and is expressed in most of the cancers associated with Epstein-Barr virus (EBV) infection including posttransplant lymphomas, Hodgkin's disease, nasopharyngeal carcinoma, and AIDS-related lymphomas. In this study, three lineages of LMP1 transgenic mice were established with LMP1 expressed under the control of the Ig heavy chain promoter and enhancer. Lymphoma developed in all three lineages, and the incidence of lymphoma increased significantly with age with lymphomas developing in 42% of transgenic mice over 18 months. The expression of LMP1 was detected at high levels in the lymphoma tissues but only at trace levels in normal lymphoid tissues. Gene rearrangement of the Ig heavy chain indicated monoclonality or oligoclonality in all lymphomas, some of the lymphoid hyperplastic spleens, and some histologically normal spleens. These data reveal that LMP1, without the expression of other EBV genes, is oncogenic in vivo and indicate that LMP1 is a major contributing factor to the development of EBV-associated lymphomas.

MeSH Terms
Animals Enhancer Elements, Genetic Gene Expression Gene Rearrangement, B-Lymphocyte, Heavy Chain Genes, Immunoglobulin Genes, Viral Herpesvirus 4, Human/genetics,pathogenicity Humans Lymphoma, B-Cell/etiology,genetics,virology Mice Mice, Transgenic Oncogenes Promoter Regions, Genetic RNA, Messenger/genetics,metabolism Viral Matrix Proteins/genetics
Chemicals
EBV-associated membrane antigen, Epstein-Barr virus RNA, Messenger Viral Matrix Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Kulwichit W
Lineberger Comprehensive Cancer Center, Microbiology and Immunology, and Pathology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.
Edwards R H
Davenport E M
Baskar J F
Godfrey V
Raab-Traub N
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.20.11963
Published
1998-09-29
Pages
11963-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC21748
Subset
IM
Grants
NCI NIH HHS · P01 CA019014 · United States
NCI NIH HHS · CA 19014 · United States
External Links
PubMed source DOI: 10.1073/pnas.95.20.11963 PMC Full Text View journal details
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