Epstein-Barr virus BHRF1 protein protects against cell death induced by DNA-damaging agents and heterologous viral infection

Abstract

The BHRF1 open reading frame of Epstein-Barr virus (EBV) codes for a 191-amino-acid protein that is expressed at high levels in productively infected cells and in certain latently infected cells. The BHRF1-coding sequences are conserved among all EBV isolates examined. BHRF1 shares a distant colinear amino acid sequence homology with the protein coded by the Bcl-2 protooncogene which suppresses apoptotic cell death induced by multiple stimuli. We have established Chinese hamster ovary cell lines which constitutively express the BHRF1 protein and show that this viral protein can protect against apoptosis induced by the DNA-damaging agents cisplatin, etoposide, and mitomycin C. The BHRF1 protein also strongly suppresses DNA fragmentation induced by an adenovirus E1B 19K deletion mutant. These results suggest that the BHRF1 protein is functionally similar to Bcl-2 and adenovirus E1B 19-kDa proteins. Since BHRF1 efficiently suppresses apoptosis induced by anti-cancer agents, its expression may have important implications for the chemotherapy of EBV-induced malignancies.