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ISSN
1672-9145
Acta Biochim Biophys Sin
2005, 37(4): 215–220
CN 31-1940/Q
Induction of Epstein-Barr Virus Lytic Replication by Recombinant
Adenoviruses Expressing the Zebra Gene with EBV Specific Promoters
Lu CHEN, Juan YIN, Yi CHEN, and Jiang
ZHONG*
Department of Microbiology and Microbial Engineering, School of Life
Sciences, Fudan University, Shanghai 200433, China
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.
Key words Epstein-Barr virus;
recombinant adenovirus; lytic replication; cancer
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Received: December 22, 2004 Accepted: February 18,
2005
This work was supported by a grant from the “Shuguang” Program of
the Shanghai Municipal Education Foundation
*Corresponding author: Tel, 86-21-55664332; Fax, 86-21-65650149;
E-mail, [email protected]