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Rôle des virus EBV et VIH dans la formation de la translocation chromosomique t(8;14) du Lymphome de Burkitt

Abstract : Abstract: Burkitt's lymphoma is a B cell non-Hodgkin's lymphoma characterized in 80% of cases by a chromosomal translocation involving the MYC oncogene on chromosome 8 and the immunoglobulin heavy chain gene IGH on chromosome 14. The development of this lymphoma is intricately linked to the EBV virus, almost always present in endemic forms, and to HIV, which defines a clinical entity. However, little is known about the role played by these viruses in translocation formation. Simultaneous double-strand breaks, non-homologous repair of these breaks, and spatial proximity are the conditions necessary for two loci to form a translocation. We thus investigated the effect of EBV viruses on these three conditions in B lymphocytes. Our results show that EBV reactivation in latently infected B lymphocytes increases the spatial proximity between MYC and IGH, normally located in different compartments. Specific DNA damage on MYC locus seems to induce this relocation of MYC next to IGH in a MRE11-dependant mechanism. We also show that the HIV1-Tat protein can enter B cells and induce an aberrant expression of the AICDA gene increasing the risk of simultaneous DNA double strand breaks on MYC and IGH loci. This work provides evidence for the direct involvement of the EBV lytic cycle in t (8; 14) formation and strengthens previously described data on of HIV1-Tat’s role in this translocation.
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Submitted on : Wednesday, June 30, 2021 - 5:57:29 PM
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Fatimata Bintou Sall. Rôle des virus EBV et VIH dans la formation de la translocation chromosomique t(8;14) du Lymphome de Burkitt. Biochimie, Biologie Moléculaire. Université Paris-Saclay; Université Cheikh Anta Diop (Dakar), 2021. Français. ⟨NNT : 2021UPASL034⟩. ⟨tel-03275207⟩

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