ULTRASTRUCTURAL-LOCALIZATION OF BHRF1 - AN EPSTEIN-BARR-VIRUS GENE-PRODUCT WHICH HAS HOMOLOGY WITH BCL-2

BHRF1 is an Epstein-Barr virus encoded protein which has a 38% sequenc e similarity with bcl-2 over the carboxyl portion. Like bcl-2, BHRF1 h as been shown to suppress programmed cell death from apoptosis. Previo usly BHRF1 has been detected in mitochondrial, microsomal, and nuclear compartments by cell fractionation analysis. In this study we have us ed the technique of immunoelectron microscopy to define the ultrastruc tural distribution of the BHRF1 product in the EBV converted cell line s B95.8 and P3HR-1. The BHRF1 product was localized at the periphery o f the mitochondria in a pattern similar to that of bcl-2 and by analog y with bcl-2 this is likely to be the functional destination. Sequence analysis of the BHRF1 protein disclosed similarity with the recently described bcl-2 homologues bcl-x (32%) and bar (34%) over the carboxyl portion, with several domains of complete identity. BHRF1 appears to be a member of a gene family involved in the regulation of programmed cell death. The identity between BHRF1 and bcl-2, an apparent shared a bility to abrogate apoptosis, and the common ultrastructural localizat ion is compelling and suggests that bcl-2 and BHRF1 are both functiona lly and mechanistically similar.