Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Antiviral Res. 2010 Mar;85(3):490-5. doi: 10.1016/j.antiviral.2009.12.002. Epub 2009 Dec 5.
Epstein-Barr virus (EBV) expresses two transcription factors, Rta and Zta, during the immediate-early stage of the lytic cycle to activate the transcription of viral lytic genes. Our immunoblotting and flow cytometry analyses find that moronic acid, found in galls of Rhus chinensis and Brazilian propolis, at 10microM inhibits the expression of Rta, Zta, and an EBV early protein, EA-D, after lytic induction with sodium butyrate. This study also finds that moronic acids inhibits the capacity of Rta to activate a promoter that contains an Rta-response element, indicating that moronic acid interferes with the function of Rta. On the other hand, moronic acid does not appear to influence with the transactivation function of Zta. Therefore, the lack of expression of Zta and EA-D after moronic acid treatment is attributable to the inhibition of the transactivation functions of Rta. Because the expression of Zta, EA-D and many EBV lytic genes depends on Rta, the treatment of P3HR1 cells with moronic acid substantially reduces the numbers of EBV particles produced by the cells after lytic induction. This study suggests that moronic acid is a new structural lead for anti-EBV drug development.
EBV 病毒在裂解周期的早期表达两个转录因子 Rta 和 Zta，以激活病毒裂解基因的转录。我们的免疫印迹和流式细胞术分析发现，来自盐肤木虫瘿和巴西蜂胶的熊果酸在 10μM 时，在经丁酸钠诱导裂解后，能抑制 Rta、Zta 和 EBV 早期蛋白 EA-D 的表达。本研究还发现，熊果酸能抑制含有 Rta 反应元件的启动子的 Rta 激活能力，表明熊果酸干扰了 Rta 的功能。另一方面，熊果酸似乎并不影响 Zta 的转录激活功能。因此，熊果酸处理后 Zta 和 EA-D 的表达缺失归因于 Rta 转录激活功能的抑制。因为 Zta、EA-D 和许多 EBV 裂解基因的表达依赖于 Rta，所以用熊果酸处理 P3HR1 细胞后，在经裂解诱导后，细胞产生的 EBV 颗粒数量会大大减少。本研究表明，熊果酸是一种新的抗 EBV 药物研发的结构先导物。
