PMID- 8627701 OWN - NLM STAT- MEDLINE DCOM- 19960627 LR - 20200724 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 70 IP - 3 DP - 1996 Mar TI - Cyclic AMP-responsive element-dependent activation of Epstein-Barr virus zebra promoter by human herpesvirus 6. PG - 1784-91 AB - We have recently shown that infection of Epstein-Barr virus (EBV) genome-positive B cells by human herpesvirus 6 (HHV-6) results in the expression of the immediate-early EBV Zebra gene, followed by virus replication (L. Flamand, I. Stefanescu, D. V. Ablashi, and J. Menezes, J. Virol. 67:6768-6777, 1993). Here we show that HHV-6 upregulates Zebra gene transcription through a cyclic AMP-responsive element (CRE) located within the Zebra promoter (Zp). Using human B- or T-cell lines transfected with ZpCat reporter gene constructs, we demonstrate that a region designated the ZII domain of Zp is the target of HHV-6 transactivation. Mutation of the consensus AP-1/CRE site within ZII abolished the inducibility of Zp by HHV-6, whereas positioning of the ZII domain upstream of the beta-globin minimal promoter conferred responsiveness following HHV-6 infection. Binding of these factors to ZII was prevented by oligonucleotides containing CRE but not by AP-1 consensus sequences. Antibodies against CRE-binding (CREB) protein but not against c-Fos or c-Jun were able to supershift the DNA-protein complex, identifying the nature of the transcription factor which binds to ZII as a member of the CREB family of proteins. Finally, transfection of CREB protein and protein kinase A expression vectors were found to activate Zp in Jurkat cells, suggesting that phosphorylated form of CREB protein can play a determining role in the EBV reactivation process. FAU - Flamand, L AU - Flamand L AD - Laboratory of Immunovirology, University of Montreal, Quebec, Canada. FAU - Menezes, J AU - Menezes J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (BZLF1 protein, Herpesvirus 4, Human) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (DNA, Viral) RN - 0 (DNA-Binding Proteins) RN - 0 (Nucleic Acid Synthesis Inhibitors) RN - 0 (RNA, Messenger) RN - 0 (RNA, Viral) RN - 0 (Trans-Activators) RN - 0 (Transcription Factor AP-1) RN - 0 (Viral Proteins) RN - N919E46723 (Phosphonoacetic Acid) SB - IM MH - B-Lymphocytes/cytology/virology MH - Base Sequence MH - Cell Line MH - Cyclic AMP Response Element-Binding Protein/*metabolism MH - DNA, Viral MH - DNA-Binding Proteins/*genetics/metabolism MH - Gene Expression Regulation, Viral MH - Herpesvirus 6, Human/*physiology MH - Humans MH - Kinetics MH - Molecular Sequence Data MH - Nucleic Acid Synthesis Inhibitors MH - Phosphonoacetic Acid/pharmacology MH - Phosphorylation MH - *Promoter Regions, Genetic MH - RNA, Messenger MH - RNA, Viral MH - T-Lymphocytes/cytology/virology MH - Trans-Activators/*genetics/metabolism MH - Transcription Factor AP-1/metabolism MH - *Transcriptional Activation MH - *Viral Proteins PMC - PMC190004 EDAT- 1996/03/01 00:00 MHDA- 1996/03/01 00:01 PMCR- 1996/03/01 CRDT- 1996/03/01 00:00 PHST- 1996/03/01 00:00 [pubmed] PHST- 1996/03/01 00:01 [medline] PHST- 1996/03/01 00:00 [entrez] PHST- 1996/03/01 00:00 [pmc-release] AID - 10.1128/JVI.70.3.1784-1791.1996 [doi] PST - ppublish SO - J Virol. 1996 Mar;70(3):1784-91. doi: 10.1128/JVI.70.3.1784-1791.1996.