Structural Basis for Apoptosis Inhibition by Epstein-Barr Virus BHRF1
- Author(s)
- Kvansakul, M; Wei, AH; Fletcher, JI; Willis, SN; Chen, L; Roberts, AW; Huang, DCS; Colman, PM;
- Details
- Publication Year 2010-12,Volume 6,Issue #12,Page -
- Journal Title
- PLOS PATHOGENS
- Publication Type
- Journal Article
- Abstract
- Epstein-Barr virus (EBV) is associated with human malignancies, especially those affecting the B cell compartment such as Burkitt lymphoma. The virally encoded homolog of the mammalian pro-survival protein Bcl-2, BHRF1 contributes to viral infectivity and lymphomagenesis. In addition to the pro-apoptotic BH3-only protein Bim, its key target in lymphoid cells, BHRF1 also binds a selective sub-set of pro-apoptotic proteins (Bid, Puma, Bak) expressed by host cells. A consequence of BHRF1 expression is marked resistance to a range of cytotoxic agents and in particular, we show that its expression renders a mouse model of Burkitt lymphoma untreatable. As current small organic antagonists of Bcl-2 do not target BHRF1, the structures of it in complex with Bim or Bak shown here will be useful to guide efforts to target BHRF1 in EBV-associated malignancies, which are usually associated with poor clinical outcomes.
- Publisher
- PUBLIC LIBRARY SCIENCE
- Keywords
- PROGRAMMED CELL-DEATH; PROSURVIVAL BCL-2 PROTEINS; BH3 DOMAINS; TRANSGENIC MICE; BAX; HOMOLOG; FAMILY; MYC; BIM; LIGANDS
- Publisher's Version
- https://doi.org/10.1371/journal.ppat.1001236
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2010-12-01 12:00:00