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Isolation and Quantification of Epstein-Barr Virus from the P3HR1 Cell Line
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Inhibition of Epstein-Barr virus reactivation by the flavonoid apigenin
Chung-Chun Wu1, Chih-Yeu Fang2,3, Yu-Jhen Cheng2
1National Institute of Cancer Research, National Health Research Institutes, No.35, Keyan Road, Zhunan Miaoli, Miaoli County, Taiwan. chungcwu@nhri.org.tw.
Background:
Lytic reactivation of EBV has been reported to play an important role in human diseases, including NPC carcinogenesis. Inhibition of EBV reactivation is considered to be of great benefit in the treatment of virus-associated diseases. For this purpose, we screened for inhibitory compounds and found that apigenin, a flavonoid, seemed to have the ability to inhibit EBV reactivation.
Methods:
We performed western blotting, immunofluorescence and luciferase analyses to determine whether apigenin has anti-EBV activity.
Results:
Apigenin inhibited expression of the EBV lytic proteins, Zta, Rta, EAD and DNase in epithelial and B cells. It also reduced the number of EBV-reactivating cells detectable by immunofluorescence analysis. In addition, apigenin has been found to reduce dramatically the production of EBV virions. Luciferase reporter analysis was performed to determine the mechanism by which apigenin inhibits EBV reactivation: apigenin suppressed the activity of the immediate-early (IE) gene Zta and Rta promoters, suggesting it can block initiation of the EBV lytic cycle.
Conclusion:
Taken together, apigenin inhibits EBV reactivation by suppressing the promoter activities of two viral IE genes, suggesting apigenin is a potential dietary compound for prevention of EBV reactivation.
Insights
Apigenin, a dietary flavonoid, effectively inhibits Epstein-Barr virus (EBV) reactivation by suppressing key viral gene promoters. This finding suggests apigenin
Area of Science:
- Virology
- Molecular Biology
- Natural Product Chemistry
Background:
- Epstein-Barr virus (EBV) lytic reactivation is implicated in human diseases, notably nasopharyngeal carcinoma (NPC) carcinogenesis.
- Inhibiting EBV reactivation offers therapeutic benefits for virus-associated diseases.
- A screen for inhibitory compounds identified apigenin, a flavonoid, as a potential inhibitor of EBV reactivation.
Purpose of the Study:
- To investigate the anti-EBV activity of apigenin.
- To determine if apigenin can inhibit EBV reactivation and elucidate its mechanism of action.
Main Methods:
- Western blotting and immunofluorescence assays were employed to assess EBV protein expression and cell reactivation.
- Luciferase reporter assays were utilized to analyze the effect of apigenin on viral gene promoter activity.
Main Results:
- Apigenin significantly inhibited the expression of EBV lytic proteins (Zta, Rta, EAD, DNase) in both epithelial and B cells.
- A reduction in EBV-reactivating cells and a dramatic decrease in EBV virion production were observed with apigenin treatment.
- Apigenin suppressed the promoter activity of EBV immediate-early genes Zta and Rta, indicating blockage of lytic cycle initiation.
Conclusions:
- Apigenin inhibits EBV reactivation by suppressing the promoter activities of viral immediate-early genes Zta and Rta.
- These findings highlight apigenin as a potential dietary compound for the prevention of EBV reactivation.
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