Structural Basis for Apoptosis Inhibition by Epstein-Barr Virus BHRF1

PLoS Pathogens

Lin Chen¹  David C. S. Huang¹  Marc Kvansakul²  Andrew W. Roberts²  Peter M. Colman²  Simon N. Willis²  Jamie I. Fletcher²  Andrew H. Wei² 

[1] Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia;The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

关键词: Apoptosis;    Mouse models;    Epstein-Barr virus;    Burkitt's lymphoma;    Mitochondria;    Cancer treatment;    Flow cytometry;    B cells;   

DOI  :  10.1371/journal.ppat.1001236

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY