Format

Send to

Choose Destination
PLoS Pathog. 2010 Dec 23;6(12):e1001236. doi: 10.1371/journal.ppat.1001236.

Structural basis for apoptosis inhibition by Epstein-Barr virus BHRF1.

Author information

1
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.

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.

PMID:
21203485
PMCID:
PMC3009601
DOI:
10.1371/journal.ppat.1001236
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center