title: Induction of Epstein-Barr virus lytic replication by recombinant adenoviruses expressing the zebra gene with EBV specific promoters.
abstract: The latent Epstein-Barr virus (EBV) is found in the cells of many tumors. For example, EBV is detectable in almost all cases, and in almost all tumor cells, of non-keratinizing nasopharyngeal carcinoma. Activating the latent virus, which will result in its lytic replication and the death of tumor cells, is a potential approach for the treatment of EBV-associated cancers. In this study, three recombinant adenoviruses were constructed to express the Zebra gene, an EBV gene responsible for switching from the latent state to lytic replication. EBV-specific promoters were used in order to limit Zebra expression in EBV-positive cells, and reduce the potential side effects. The EBV promoters used were Cp, Zp and a dual promoter combining both promoters, CpZp. The Zebra protein was detected in HEK293 cells as well as the EBV-positive D98-HR1 cells infected with recombinant viruses. An EBV lytic replication early antigen, EA-D, was also detected in infected D98-HR1, implying the initiation of lytic replication. In the cell viability assay, Zebra-expressing adenoviruses had little effect on EBV-negative HeLa cells, while significantly reducing the cell viability and proliferation of D98-HR1 cells. The results indicate that EBV virus promoters can be used in adenovirus vectors to express the Zebra gene and induce EBV lytic replication in D98-HR1 cells.
authors.affiliation: Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.forename: Juan
authors.initials: J
authors.lastname: Yin
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhong
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D005818:Genetic Engineering / Q000379:methods*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011995:Recombination, Genetic / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism*; D014779:Virus Replication / Q000235:genetics*
chemical_list: C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D015534:Trans-Activators; D014764:Viral Proteins