Inhibition of the Epstein-Barr virus lytic cycle by moronic acid.
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.
Chang
Fang-Rong
FR
Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Hsieh
Yi-Chung
YC
Chang
Yung-Fu
YF
Lee
Kuo-Hsiung
KH
Wu
Yang-Chang
YC
Chang
Li-Kwan
LK
D000956:Antigens, Viral / Q000096:biosynthesis; D000998:Antiviral Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015870:Gene Expression; D004854:Herpesvirus 4, Human / Q000187:drug effects*; D006801:Humans; D017874:Immediate-Early Proteins / Q000037:antagonists & inhibitors; D015394:Molecular Structure; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D015534:Trans-Activators / Q000037:antagonists & inhibitors; D014779:Virus Replication / Q000187:drug effects*
D000956:Antigens, Viral; D000998:Antiviral Agents; C068382:BRLF1 protein, Human herpesvirus 4; C063676:BZLF1 protein, Herpesvirus 4, Human; C033305:Epstein-Barr virus early antigen; D017874:Immediate-Early Proteins; D015534:Trans-Activators; C023607:moronic acid; D009828:Oleanolic Acid