Inhibition of human cytomegalovirus immediate-early gene expression and replication by the ethyl acetate (EtOAc) fraction of Elaeocarpus sylvestris in vitro

Sohee Bae,Se Chan Kang,Yoon-Jae Song

doi:10.1186/s12906-017-1941-7

Abstract

BackgroundIn immunocompromised patients, human cytomegalovirus (HCMV) infection can lead to severe, life-threatening diseases, such as pneumonitis, hepatitis, gastrointestinal tract disease, and retinitis. We previously reported that a 70% ethanol extract of Elaeocarpus sylvestris leaves (ESE) inhibits human cytomegalovirus (HCMV) replication in vitro. In the present study, we determined the solvent fraction of ESE that inhibits HCMV replication using activity-guided fractionation.MethodsActivity-guided fractionation of ESE was performed to determine the solvent fraction that inhibits HCMV replication. Effects of solvent fractions on HCMV lytic gene expression and major immediate-early (MIE) enhancer/promoter activity were further investigated.ResultsAmong the solvent fractions tested, the EtOAc fraction of ESE markedly reduced HCMV lytic gene expression and viral replication in vitro without exerting significant cytotoxic effects against human foreskin fibroblasts (HFF). Furthermore, the EtOAc fraction negatively affected HCMV MIE enhancer/promoter activity.ConclusionOur data collectively indicate that the EtOAc fraction of ESE contains active constituents that inhibit HCMV MIE enhancer/promoter activity and viral replication. The EtOAc fraction of ESE is a good source of novel drug candidates for treatment of HCMV-associated diseases.

Highlights

In immunocompromised patients, human cytomegalovirus (HCMV) infection can lead to severe, life-threatening diseases, such as pneumonitis, hepatitis, gastrointestinal tract disease, and retinitis
Effects of Elaeocarpus sylvestris leaves (ESE) solvent fractions on HCMV replication ESE was fractionated via sequential solvent extraction, and the effects of individual fractions on HCMV replication was determined using quantitative polymerase chain reaction (qPCR) with primers specific for UL123
At a low (0.1) multiplicity of infection (MOI), HCMV replication was reduced by each solvent fraction of ESE fractions at a concentration of 50 μg/ml (Fig. 2a)

Summary

Introduction

Human cytomegalovirus (HCMV) infection can lead to severe, life-threatening diseases, such as pneumonitis, hepatitis, gastrointestinal tract disease, and retinitis. We previously reported that a 70% ethanol extract of Elaeocarpus sylvestris leaves (ESE) inhibits human cytomegalovirus (HCMV) replication in vitro. Human cytomegalovirus (HCMV) is the largest human herpesvirus with a linear double-stranded DNA genome of about 230 kb encoding 167 viral proteins [1, 2]. The HCMV lytic gene is temporally expressed in an ordered cascade involving immediate-early (IE), early (E) and late (L) gene expression. The major IE1 and 2 genes encode important regulatory proteins, such as IE1-72 kDa and IE2-86 kDa that control early and late gene expression [7]. Genes encode proteins that regulate viral DNA synthesis, while

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Conclusion