Inhibition of Epstein-Barr Virus Lytic Cycle by an Ethyl Acetate Subfraction Separated from Polygonum cuspidatum Root and Its Major Component, Emodin

Ching-Yi Yiu,Che-Jung Chang,Tsuey-Pin Lin,Dong-Bor Yeh,Yi-Jie Chen,Shih-Ying Chen,Tsai-Hsiu Yang

doi:10.3390/molecules19011258

Abstract

Polygonum cuspidatum is widely used as a medicinal herb in Asia. In this study, we examined the ethyl acetate subfraction F3 obtained from P. cuspidatum root and its major component, emodin, for their capacity to inhibit the Epstein-Barr virus (EBV) lytic cycle. The cell viability was determined by the MTT [3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide] method. The expression of EBV lytic proteins was analyzed by immunoblot, indirect immunofluorescence and flow cytometric assays. Real-time quantitative PCR was used to assess the EBV DNA replication and the transcription of lytic genes, including BRLF1 and BZLF1. Results showed that the F3 and its major component emodin inhibit the transcription of EBV immediate early genes, the expression of EBV lytic proteins, including Rta, Zta, and EA-D and reduces EBV DNA replication, showing that F3 and emodin are potentially useful as an anti-EBV drug.

Highlights

Epstein-Barr virus (EBV) is an oncogenic human herpesvirus, which infects lymphoid cells and epithelial cells [1]
Its components were analyzed by high liquid pressure chromatography and the identification of target compounds in F3 was based on their retention time and UV spectra, compared against a pure standard of emodin
We found that the peak eluting at 33.01 min could be ascribed to emodin (Figure 1)

Summary

Introduction

Epstein-Barr virus (EBV) is an oncogenic human herpesvirus, which infects lymphoid cells and epithelial cells [1]. At onset of the lytic cycle, EBV expresses two transcription factors, Rta and Zta, which are transcribed from BRLF1 and BZLF1, respectively [8]. These two proteins trigger an ordered cascade of the expression of viral lytic genes, including that of BMRF1 and BALF5, which encoded diffused early antigen (EA-D) and DNA polymerase [9]. After EBV DNA replication, late genes, such as those encoding virus capsid antigens and membrane proteins, are expressed, followed by the production mature virions [10]. Some studies have suggested that the EBV lytic cycle causes tumorigenesis by the induction of cytokines [11]

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