EPSTEIN-BARR-VIRUS (EBV) EB1 ZTA PROTEIN PROVIDED IN TRANS AND COMPETENT FOR THE ACTIVATION OF PRODUCTIVE CYCLE GENES DOES NOT ACTIVATE THEBZLF1 GENE IN THE EBV GENOME/

The Epstein-Barr Virus (EBV) gene BZLF1 encodes the transcription fact or EB1 (also known as Zta) which is essential for the switch from late ncy to the lytic cycle: EB1 expressed from a plasmid transfected into B cell lines carrying latent EBV episomes, induces a productive viral cycle. Furthermore, EB1-specific DNA-binding sequences (ZREs) have bee n found in the promoters of many EBV early genes, including the BZLF1 promoter PZ and the PR promoter. At promoter PR, bicistronic mRNAs are initiated which contain, from 5' to 3', the BRLF1 and the BZLF1 open reading frames (ORFs) encoding respectively the R and EB1 proteins. Th e current model for the activation of the EBV lytic cycle implies that downregulation of the PZ promoter activity is a key element for laten cy and that a limiting step in the activation of the productive cycle is the translation of EB1. Once made, EB1 autoactivates promoter PZ, a ctivates the PR promoter at which an mRNA coding for the EBV transcrip tion factor R is initiated and activates the EBV early genes and the O RI(lyt), due to unrestricted accessibility of the EB1-responsive eleme nts in the viral genome. We show here that EB1 expressed from a plasmi d activated most if not all of the EBV early genes in the viral genome but not its own gene, BZLF1. Moreover, transfected EB1 induced the tr anscription of the bicistronic mRNAs from which R is efficiently trans lated but not EB1. Our results demonstrate that EB1 provided in trans, although competent to activate the productive cycle genes, was not su fficient to overcome the downregulation of the PZ promoter.