Inhibition of the Epstein-Barr virus lytic cycle by Zta-targeted RNA interference

• Published in: Journal of general virology 2004-06, Vol.85 (6), p.1371-1379
• Main Authors: Chang, Yao, Chang, Shih-Shin, Lee, Heng-Huan, Doong, Shin-Lian, Takada, Kenzo, Tsai, Ching-Hwa
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Epstein-Barr virus; Fundamental and applied biological sciences. Psychology; Herpesvirus 4, Human - genetics; Herpesvirus 4, Human - physiology; Humans; Microbiology; Miscellaneous; RNA Interference; STAT1 Transcription Factor; Trans-Activators - antagonists & inhibitors; Trans-Activators - genetics; Trans-Activators - metabolism; Viral Proteins - antagonists & inhibitors; Viral Proteins - genetics; Virology; Virus Activation
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.79886-0

1 Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Room 714, Number 1, Section 1, Jen-Ai Road, Taipei, Taiwan 2 Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan Correspondence Ching-Hwa Tsai chtsai{at}ha.mc.ntu.edu.tw Epstein–Barr virus (EBV) reactivation into the lytic cycle plays certain roles in the development of EBV-associated diseases, so an effective strategy to block the viral lytic cycle may be of value to reduce the disease risk or to improve the clinical outcome. This study examined whether the EBV lytic cycle could be inhibited using RNA interference (RNAi) directed against the essential viral gene Zta. In cases of EBV reactivation triggered by chemicals or by exogenous Rta, Zta-targeted RNAi prevented the induction of Zta and its downstream genes and further blocked the lytic replication of viral genomes. This antiviral effect of RNAi was not likely to be mediated by activation of the interferon pathway, as phosphorylation of STAT1 was not induced. In addition, novel EBV-infected epithelial cells showing constitutive activation of the lytic cycle were cloned; such established lytic infection was also suppressed by Zta-targeted RNAi. These results indicate that RNAi can be used to inhibit the EBV lytic cycle effectively in vitro and could also be of potential use to develop anti-EBV treatments.