EPSTEIN-BARR VIRUS-CODED BHRF1 PROTEIN, A VIRAL HOMOLOG OF BCL-2, PROTECTS HUMAN B-CELLS FROM PROGRAMMED CELL-DEATH

Epstein-Barr virus, a human herpesvirus that persists within the B-lym phoid system, can enhance the survival potential of latently infected B cells in vitro through up-regulation of the cellular survival protei n Bcl-2. The possibility that an analogous effect is operative in lyti cally infected cells was suggested by the observation of distant seque nce homology between an Epstein-Barr virus-coded early lytic cycle pro tein, BHRF1, and Bcl-2. Here we show by gene transfer that BHRF1 resem bles Bcl-2 both in its subcellular localization and in its capacity to enhance B-cell survival. Thus confocal microscopic analysis of cells acutely cotransfected with BHRF1 and Bcl-2 expression vectors revealed substantial colocalization of the two proteins in the cytoplasm. In s ubsequent experiments, stable BHRF1 gene transfectants of Burkitt lymp homa cells paralleled Bcl-2 transfectants in their enhanced survival u nder conditions that induce cell death by apoptosis. Despite their lim ited sequence conservation, therefore, the two proteins appear to be f unctionally homologous. We suggest that BHRF1 provides an alternative, Bcl-2-independent, means of enhancing B-cell survival that may operat e during the virus lytic cycle.