22 research outputs found
Changes in the expression of fc receptor produced by induction of Epstein-Barr virus in lymphoma cell lines
Analytic Validation of a Competitive Polymerase Chain Reaction Assay for Measuring Epstein-Barr Viral Load
Induction of epstein-barr virus by a new tumor promoter, teleocidin, compared to induction by TPA
Steroids inhibit tumor promoting agent induced Epstein-Barr virus early antigens in raji cells
Mechanism of enhancement of epstein-barr virus-induced transformation of peripheral blood lymphocytes by a tumor promoter, tpa, with special reference to lowering of cytotoxicity of t cells
Large-scale purification of Epstein-Barr virus membrane antigen gp340 with a monoclonal antibody immunoabsorbent
The ZIIR Element of the Epstein-Barr Virus BZLF1 Promoter Plays a Central Role in Establishment and Maintenance of Viral Latencyâ–¿
The Epstein-Barr virus (EBV) BZLF1 gene encodes the immediate-early (IE) protein Zta, which plays a central role in regulating the switch between viral latency and lytic replication. A silencing element, ZIIR, is located between the ZID and ZII positive regulatory elements in the BZLF1 promoter Zp. We report here the phenotypes of variants of EBV strain B95.8 containing base substitution mutations in this ZIIR element. HEK293 cells infected with ZIIR mutant (ZIIRmt) virus produced at least 20-fold more viral IE Zta and Rta and early (E) EAD protein than did cells infected with the parental wild-type (WT) virus, leading to viral DNA replication and production of infectious virus. However, ZIIR mutant virus was 1/10 as efficient as WT virus in establishing proliferating B-cell clones following infection of human primary blood B cells. The ZIIRmt-infected lymphoblastoid cell lines (LCLs) that did grow out exhibited a phenotype similar to the one observed in 293 cells, including marked overproduction of IE and E gene products relative to WT-infected LCLs and lytic replication of the viral genome. Incubation of the ZIIRmt-infected LCLs with the chemical inducer 12-O-tetradecanoyl-phorbol-13-acetate (TPA) led to much greater activation of Zp than did the same treatment of WT- or ZVmt-infected LCLs. Furthermore, a protein kinase C (PKC) inhibitor, bis-indolylmaleimide, eliminated this activation by TPA. Thus, we conclude that ZIIR is a potent silencing element of Zp; it plays a key role in establishment and maintenance of EBV latency by inhibiting activation of Zp through the PKC signal transduction pathway