title: Kaempferol inhibits enterovirus 71 replication and internal ribosome entry site (IRES) activity through FUBP and HNRP proteins.
abstract: Flavonoids are associated with multiple biological and pharmacological activities, including anti-enterovirus activity. An internal ribosomal entry site (IRES) required for viral protein translation is a potential drug target for enterovirus 71 (EV71). Regulation translation initiation requires the interaction of IRES specific trans-acting host factors with viral IRES element. By evaluation of 12 flavonoids against EV71 infection, we found that (a) 7,8-dihydroxyflavone, kaempferol, quercetin, hesperetin and hesperidin exhibited more than 80% of cell survival and inhibition of EV71 infection; however, no anti-oxidative effects were noted from these flavonoids; (b) among them, only 7,8-dihydroxyflavone, kaempferol and hesperetin showed 40% of viral IRES activity; (c) kaempferol interfered with EV71 virus replication and pseudotyped virus production; and (d) FUBP1, FUBP3, HNRPD, HNRH1 and HNRPF proteins are associated with EV71 5'-UTR as shown using RNA affinity pull-down assay coupled with LC-MS/MS analysis. We firstly found that kaempferol may change the composition of these IRES associated trans-acting factors, and affect IRES function and EV71 virus replication. These studies help not only to understand the IRES function but also the mechanism by which drug induced cellular proteins are acting against EV71 infection.
authors.affiliation: Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, ROC; School of Chinese Medicine, China Medical University, Taichung, Taiwan, ROC; Department of Biotechnology, Asia University, Taichung, Taiwan, ROC.
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.affiliation: Department of Biotechnology, Asia University, Taichung, Taiwan, ROC; Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Lin
authors.affiliation: Institute of Molecular Biology, National Chung Hsing University, Taichung, Taiwan, ROC.
authors.forename: Chien-Chen
authors.initials: CC
authors.lastname: Lai
authors.affiliation: Department of Health Risk Management, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Lan
authors.affiliation: Department of Microbiology, School of Medicine, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Chih-Ho
authors.initials: CH
authors.lastname: Lai
authors.affiliation: Graduate Institute of Clinical Medical Science, Chang-Gung University, Chiayi, Taiwan, ROC.
authors.forename: Chien-Hui
authors.initials: CH
authors.lastname: Hung
authors.affiliation: Department of Pediatrics, Taichung Hospital Department of Health, Taichung, Taiwan, ROC.
authors.forename: Kai-Chung
authors.initials: KC
authors.lastname: Hsueh
authors.affiliation: Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, ROC.
authors.forename: Ting-Hsu
authors.initials: TH
authors.lastname: Lin
authors.affiliation: Department of Biotechnology, Asia University, Taichung, Taiwan, ROC.
authors.forename: Hebron C
authors.initials: HC
authors.lastname: Chang
authors.affiliation: Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, ROC; School of Chinese Medicine, China Medical University, Taichung, Taiwan, ROC; Department of Biotechnology, Asia University, Taichung, Taiwan, ROC.
authors.forename: Lei
authors.initials: L
authors.lastname: Wan
authors.affiliation: Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, ROC; School of Chinese Medicine, China Medical University, Taichung, Taiwan, ROC; Department of Biotechnology, Asia University, Taichung, Taiwan, ROC.
authors.forename: Jim Jinn-Chyuan
authors.initials: JJ
authors.lastname: Sheu
authors.affiliation: Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, ROC; School of Chinese Medicine, China Medical University, Taichung, Taiwan, ROC. Electronic address: yjlin.kath@gmail.com.
authors.forename: Ying-Ju
authors.initials: YJ
authors.lastname: Lin
keywords: Enterovirus 71; Internal ribosome entry site; Kaempferol; Trans-acting factors