EBV Conference 2008 Guangzhou - Baylor College of Medicine

80 (RegID: 1515; 1516)
Chung-Chun Wu
Institution: National Institute of Cancer Research, National Health Research Institutes
e-mail: chungcwu@nhri.org.tw
EPSTEIN-BARR VIRUS DNASE INDUCES MICRONUCLEUS FORMATION, DNA STRAND
BREAKS AND GENETIC MUTATION IN HUMAN EPITHELIAL CELLS
Chung-Chun Wu, Ming-Tsan Liu, Yu-Ting Chang, Chih-Yeu Fang, Sheng-Ping Chou,Hsin-Wei Liao,
Kuan-Lin Kuo, Shih-Lung Hsu, Yi-Ren Chen, Shu-Feng Lin, Ching-Hwa Tsai, Yao Chang, Kenzo Takada,
Jen-Yang Chen
Posterabstract:
Serological studies indicate that EBV reactivation may be associated with the development of
nasopharyngeal carcinoma (NPC). Previous investigations indicated that latent EBV infection may induce
genomic instability and contribute to the development of B cell tumor formation. In this study, we sought
to investigate whether the lytic proteins of EBV could cause the genomic instability in human epithelial
cells. In EBV-harboring NPC cells, induction of EBV lytic replication by
12-o-tetradecanoyl-phorbol-1,3-acetate and sodium butyrate or the EBV immediate early protein Zta
induced DNA stand breaks and micronucleus formation. Transfection of a plasmid expressing Zta siRNA
prior to induction of EBV replication prevented these changes. Furthermore, examination of a panel of
EBV lytic proteins identified EBV DNase as a potent activator which induced DNA strand breaks and
micronucleus formation in a dose-dependent manner. However, the expression of a DNase-null plasmid
did not show similar effects. In addition, this enzyme also increased the microsatellite instability and
frequency of genetic mutation in human epithelial cells. We propose that reactivation of EBV can induce
genomic instability through lytic proteins such as EBV DNase, causing DNA damage, micronucleus
formation, microsatellite instability and genetic mutation, and may contribute subsequently to the
tumorigenesis of human epithelial cells.
EBV Conference 2008 Guangzhou
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