Lymphoid hyperplasia and lymphoma in transgenic mice expressing the small non-coding RNA, EBER1 of Epstein-Barr virus

Repellin, C.E., Tsimbouri, P.M. , Philbey, A.W. and Wilson, J.B. (2010) Lymphoid hyperplasia and lymphoma in transgenic mice expressing the small non-coding RNA, EBER1 of Epstein-Barr virus. PLoS ONE, 5(2), e9092. (doi: 10.1371/journal.pone.0009092)

Abstract

Background. Non-coding RNAs have critical functions in diverse biological processes, particularly in gene regulation. Viruses, like their host cells, employ such functional RNAs and the human cancer associated Epstein-Barr virus (EBV) is no exception. Nearly all EBV associated tumours express the EBV small, non-coding RNAs (EBERs) 1 and 2, however their role in viral pathogenesis remains largely obscure.Methodology/Principal FindingsTo investigate the action of EBER1 in vivo, we produced ten transgenic mouse lines expressing EBER1 in the lymphoid compartment using the mouse immunoglobulin heavy chain intronic enhancer E++. Mice of several of these E++EBER1 lines developed lymphoid hyperplasia which in some cases proceeded to B cell malignancy. The hallmark of the transgenic phenotype is enlargement of the spleen and mesenteric lymph nodes and in some cases enlargement of the thymus, liver and peripheral lymph nodes. The tumours were found to be of B cell origin and showed clonal IgH rearrangements. In order to explore if EBER1 would cooperate with c-Myc (deregulated in Burkitt's lymphoma) to accelerate lymphomagenesis, a cross-breeding study was undertaken with E++EBER1 and E++Myc mice. While no significant reduction in latency to lymphoma onset was observed in bi-transgenic mice, c-Myc induction was detected in some E++EBER1 single transgenic tumours, indicative of a functional cooperation. Conclusions/SignificanceT his study is the first to describe the in vivo expression of a polymerase III, non-coding viral gene and demonstrate its oncogenic potential. The data suggest that EBER1 plays an oncogenic role in EBV associated malignant disease.

• Item Type: Articles
• Additional Information: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Tsimbouri, Dr Monica and Wilson, Professor Joanna and Philbey, Dr Adrian
• Authors: Repellin, C.E., Tsimbouri, P.M., Philbey, A.W., and Wilson, J.B.
• College/School: College of Medical Veterinary and Life Sciences > School of Life Sciences; College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine; College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• ISSN (Online): 1932-6203
• Published Online: 08 February 2010
• Copyright Holders: © 2010 Repellin et al.
• First Published: First published in PLoS ONE 2010 5(2): e9092
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
41536	1	An investigation into the action of the EBV small RNAs in vivo	Joanna Wilson	Wellcome Trust (WELLCOME)	078519/Z/05/Z	Life Sciences Biomolecular Science