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Detection of clonal EBV episomes in lymphoproliferations as a diagnostic tool

Leukemia volume 16, pages 1572–1573 (2002)Cite this article

Epstein–Barr virus1 (EBV) belongs to the family of gamma herpes viruses and was first identified in endemic African Burkitt's lymphoma by Epstein and Barr. The virus is present in the majority of the population and is known to cause mononucleosis infectiosa, which is characterized by proliferation of cytotoxic T lymphocytes in response to EBV-containing B lymphocytes. Later EBV was found to be closely associated with a large variety of human malignancies, ranging from nasopharyngeal carcinomas to post-transplant (B cell) lymphomas and AIDS-associated lymphomas, but also T and NK cell lymphomas and even Hodgkin's disease (reviewed in Su and Chen2).

 The EBV genome is a ∼172 kb linear molecule, which circularizes into an extrachromosomal molecule (episomal form) when the virus enters the nucleus of a target cell. Entry into a target cell is probably mediated via the complement receptor type 2 (CR2 or CD21 antigen), which is primarily expressed on B lymphocytes, but also on subsets of thymocytes and activated T/NK cells. Infection by EBV has been shown to drive transformation of B lymphocytes. In the host cell the virus probably primarily resides in its episomal form, which can be replicated by the host DNA polymerase, but (non-random) linear integration into the host genome might also occur. Nevertheless, the multiple episomal copies in an infected cell exceed the single or few linear genomes that may be present. As a consequence the episomes are more easily detected. Circularization into episomes is mediated via direct terminal repeats (TR) of approximately 500 bp long. Due to variation in the number of TR sequences at the ends of the viral genome, there is considerable heterogeneity between infected cells with respect to the numbers of the fused termini (probably up to 15–20) on the episomal EBV genome. In contrast, in the case of a monoclonal cell population, all daughter cells that are derived from a single EBV-harboring cell will contain identical TR numbers in their EBV episomes. This phenomenon allows the detection of monoclonal EBV genome, eg through restriction fragment analysis, and thereby to assess or exclude the clonal character of the EBV-infected cell population.3

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  1. Department of Immunology, University Hospital Rotterdam/Erasmus University Rotterdam, The Netherlands

    AW Langerak, E Moreau, EJ van Gastel-Mol, M van der Burg & JJM van Dongen

  2. Heilig-Hartziekenhuis, Roeselare, Belgium

    E Moreau

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  1. AW Langerak
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  2. E Moreau
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Langerak, A., Moreau, E., van Gastel-Mol, E. et al. Detection of clonal EBV episomes in lymphoproliferations as a diagnostic tool. Leukemia 16, 1572–1573 (2002). https://doi.org/10.1038/sj.leu.2402519

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