Epstein-Barr virus (EBV) EB1/Zta protein provided in trans and competent for the activation of productive cycle genes does not activate the BZLF1 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 latency 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 been 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. The current model for the activation of the EBV lytic cycle implies that downregulation of the PZ promoter activity is a key element for latency and that a limiting step in the activation of the productive cycle is the translation of EB1. Once made, EB1 autoactivates promoter PZ, activates the PR promoter at which an mRNA coding for the EBV transcription factor R is initiated and activates the EBV early genes and the ORIlyt, due to unrestricted accessibility of the EB1-responsive elements in the viral genome. We show here that EB1 expressed from a plasmid 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 transcription of the bicistronic mRNAs from which R is efficiently translated but not EB1. Our results demonstrate that EB1 provided in trans, although competent to activate the productive cycle genes, was not sufficient to overcome the downregulation of the PZ promoter.
Le Roux
F
F
Unité de virologie humaine, ENS-INSERM, U412, Ecole Normale Supérieure de Lyon, France.
Sergeant
A
A
Corbo
L
L
D001483:Base Sequence; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D004279:DNA, Viral; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D017781:Genes, Immediate-Early; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D014764:Viral Proteins; D014779:Virus Replication / Q000235:genetics
C068382:BRLF1 protein, Human herpesvirus 4; C063676:BZLF1 protein, Herpesvirus 4, Human; D002087:Butyrates; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins; D020148:Butyric Acid