Epstein-Barr virus nuclear antigen-1 renders lymphocytes responsive to IL-2 but not IL-15 for survival

Tsimbouri, P. , Al-Sheikh, Y., Drotar, M. E., Cushley, W. and Wilson, J.B. (2008) Epstein-Barr virus nuclear antigen-1 renders lymphocytes responsive to IL-2 but not IL-15 for survival. Journal of General Virology, 89(11), pp. 2821-2832. (doi:10.1099/vir.0.83296-0)

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Publisher's URL: http://dx.doi.org/10.1099/vir.0.83296-0

Abstract

Epstein-Barr virus nuclear antigen-1 (EBNA-1) is the only latent protein expressed in all virus-associated tumours. It plays a critical role in viral propagation and in the replication, episomal maintenance and partitioning of the viral genome. However, its tumorigenic potential is debated. We have previously shown that lymphocytes from a tumour-prone, EBNA-1-expressing, transgenic mouse line show increased responsiveness to interleukin-2 (IL-2). It was important to determine whether this property was unique to the transgenic line or whether it is a general consequence of EBNA-1 expression in B cells. In order to distinguish between these possibilities, explanted lymphocytes from two independent transgenic mouse lines were examined. The lymphocytes from both lines showed enhanced proliferation rates compared with controls. The transgenic lymphocytes survived for extended periods in culture, dependent on the dose of IL-2, while IL-15 (the receptor of which shares the {beta} and{gamma} chain components of the IL-2 receptor) induced little effect. In accordance with this, transgenic B cells showed enhanced induction of expression of the IL-2 receptor{alpha} chain (CD25), which modulates affinity for the ligand. As this phenotype is evident in lymphocytes from mice of both lines, it is necessarily independent of any transgene insertion site effects and may be attributed to EBNA-1 expression. Furthermore, 10/12 tumour-bearing transgenic mice had elevated IL-2 levels in serum and 4/6 tumours were CD25 positive. IL-2 is normally produced by activated T cells in vivo; thus, chronic immune activation or modulation could elicit this unique mode of virus-infected cell survival

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Wilson, Professor Joanna and Cushley, Professor William and Tsimbouri, Dr Monica
Authors: Tsimbouri, P., Al-Sheikh, Y., Drotar, M. E., Cushley, W., and Wilson, J.B.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Journal of General Virology
Publisher:Society for General Microbiology
ISSN:0022-1317
ISSN (Online):1465-2099

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