Séquençage du génome complet du virus d’Epstein-Barr dans des prélèvements issus de lymphomes T angio-immunoblastiques

Abstract : More than 90% of the world's population is infected by Epstein-Barr virus (EBV), a human herpesvirus. EBV is thought to be implicated in the pathogenesis of several human malignancies including epithelial tumors such as nasopharyngeal and gastric carcinomas as well as lymphoproliferative diseases such as Burkitt's lymphoma, NK/T lymphomas and some Hodgkin lymphomas. In angioimmunoblastic T-cell lymphoma (AITL), a peripheral neoplasm of follicular helper T (TFH) cells, a recurrent finding is the presence of EBV-positive B lymphocytes at the beginning of the disease. However, whether this EBV infection of B cells plays a role in AITL pathogenesis remains unclear. In this context, our work aimed to determine if the EBV associated with the AITL presented an oncogenic profile allowing us to consider its role in this pathology. To do this, we sequenced the whole EBV genomes in AIL samples and compared the results to those obtained for other lymphomas (B, NK / T) as well as to previously published sequences. Sequencing was first performed on 7 EBV-positive cell lines to validate the technique, and then was applied to lymphadenopathy specimens from 40 patients with lymphoproliferative disease, of whom 20 had AITL. Enrichment of the viral genome was performed by capture using specific EBV genome probes. The libraries were synthesized and sequenced on Illumina MiSeq and NextSeq platforms. In a second step, we performed de novo assembly and determined the sequence of the virus in each sample. The data obtained were analyzed bioinformatically. Interestingly, the virus was found to be clonal or quasi-clonal in AITL, while B cells were in some cases polyclonal. In addition, the mutational pattern was similar to other EBV-associated lymphomas, especially at the level of the target epitopes of immune cells suggesting a process of selection of the viral strain identical to that of a clone tumor associated with EBV. This could play an important role in the virus escape from the immune system in this context. The presence of polyclonal B cells with clonal EBV in a clonal tumor T cell compartment could be a dual tumor selection; or that is endogenous T and exogenous clonal EBV, and could therefore suggest the existence of a cross-talk between B-T cells.
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Racha Bahri. Séquençage du génome complet du virus d’Epstein-Barr dans des prélèvements issus de lymphomes T angio-immunoblastiques. Médecine humaine et pathologie. Université de Limoges, 2017. Français. ⟨NNT : 2017LIMO0106⟩. ⟨tel-01963285⟩

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