EBV BCL-2 homologue BHRF1 drives chemoresistance and lymphomagenesis by inhibiting multiple cellular pro-apoptotic proteins

Leah Fitzsimmons; Rachel Cartlidge; Catherine Chang; Nenad Sejic; Laura CA Galbraith; Chathura D Suraweera; Deborah Croom-Carter; Grant Dewson; Rosemary J Tierney; Andrew Bell; Clare Shannon-Lowe; Marco J Herold; Alan B Rickinson; Peter M Colman; David CS Huang; Andreas Strasser; Marc Kvansakul; Martin Rowe; Gemma L Kelly

Journal article

EBV BCL-2 homologue BHRF1 drives chemoresistance and lymphomagenesis by inhibiting multiple cellular pro-apoptotic proteins

Leah Fitzsimmons, Rachel Cartlidge, Catherine Chang, Nenad Sejic, Laura CA Galbraith, Chathura D Suraweera, Deborah Croom-Carter, Grant Dewson, Rosemary J Tierney, Andrew Bell, Clare Shannon-Lowe, Marco J Herold, Alan B Rickinson, Peter M Colman, David CS Huang, Andreas Strasser, Marc Kvansakul, Martin Rowe, Gemma L Kelly

Cell Death & Differentiation | NATURE PUBLISHING GROUP | Published : 2020

DOI: 10.1038/s41418-019-0435-1

Abstract

Epstein-Barr virus (EBV), which is ubiquitous in the adult population, is causally associated with human malignancies. Like many infectious agents, EBV has evolved strategies to block host cell death, including through expression of viral homologues of cellular BCL-2 pro-survival proteins (vBCL-2s), such as BHRF1. Small molecule inhibitors of the cellular pro-survival BCL-2 family proteins, termed 'BH3-mimetics', have entered clinical trials for blood cancers with the BCL-2 inhibitor venetoclax already approved for treatment of therapy refractory chronic lymphocytic leukaemia and acute myeloid leukaemia in the elderly. The generation of BH3-mimetics that could specifically target vBCL-2 prot..

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