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Epstein–Barr virus–associated Burkitt lymphomagenesis selects for downregulation of the nuclear antigen EBNA2

Nature Medicine volume 8, pages 1098–1104 (2002)Cite this article

Abstract

Epstein–Barr virus (EBV) is etiologically linked to endemic Burkitt lymphoma (BL), but its contribution to lymphomagenesis, versus that of the chromosomal translocation leading to c-myc gene deregulation, remains unclear. The virus's growth-transforming (Latency III) program of gene expression is extinguished in tumor cells, and only a single viral protein, the EBV nuclear antigen (EBNA)1, is expressed via the alternative Latency I program. It is not known if BL arises from a B-cell subset in which EBV naturally adopts a Latency I infection or if a clone with limited antigen expression has been selected from an EBV-transformed Latency III progenitor pool. Here we identify a subset of BL tumors in which the Latency III-associated EBNA promoter Wp is active and most EBNAs are expressed, but where a gene deletion has specifically abrogated the expression of EBNA2. This implies that BL can be selected from a Latency III progenitor and that the principal selection pressure is for downregulation of the c-Myc antagonist EBNA2.

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Figure 1: Cell-surface phenotype and EBV gene transcription in standard and atypical BL lines versus LCLs.
Figure 2: EBV gene expression in standard and atypical BL lines versus LCLs.
Figure 3: EBV latent protein expression and c-Myc levels in standard and atypical BL lines versus LCLs.
Figure 4: Antigen processing in Sal-BL and Oku-BL cell lines versus the Sal sp-LCL.
Figure 5: EBV latent gene expression in representative BL biopsy samples.
Figure 6: EBNA2 gene deletion in atypical BL cell lines.

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Acknowledgements

We thank A. Leese for performing the Elispot assays; D. Croom-Carter for assistance with immunoblotting and D. Morton for tumor biopsies and matching blood samples. This work was supported by Cancer Research UK and by a Cancer Research UK-funded studentship to G.K.

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  1. Cancer Research UK Institute for Cancer Studies, The University of Birmingham, Edgbaston, Birmingham, UK

    Gemma Kelly, Andrew Bell & Alan Rickinson

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Correspondence to Alan Rickinson.

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Kelly, G., Bell, A. & Rickinson, A. Epstein–Barr virus–associated Burkitt lymphomagenesis selects for downregulation of the nuclear antigen EBNA2. Nat Med 8, 1098–1104 (2002). https://doi.org/10.1038/nm758

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