Structural Basis for Apoptosis Inhibition by Epstein-Barr Virus BHRF1 Academic Article uri icon

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.

authors

  • Kvansakul, Marc
  • Wei, Andrew H
  • Fletcher, Jamie I
  • Willis, Simon N
  • Chen, Lin
  • Roberts, Andrew W
  • Huang, David CS
  • Colman, Peter M

publication date

  • December 1, 2010