Kaempferol inhibits enterovirus 71 replication and internal ribosome entry site (IRES) activity through FUBP and HNRP proteins

Fuu-Jen Tsai; Cheng-Wen Lin; Chien-Chen Lai; Yu-Ching Lan; Chih-Ho Lai; Chien-Hui Hung; Kai-Chung Hsueh; Ting-Hsu Lin; Hebron C Chang; Lei Wan; Jim Jinn-Chyuan Sheu; Ying-Ju Lin

doi:10.1016/j.foodchem.2011.03.022

Kaempferol inhibits enterovirus 71 replication and internal ribosome entry site (IRES) activity through FUBP and HNRP proteins

Food Chem. 2011 Sep 15;128(2):312-22. doi: 10.1016/j.foodchem.2011.03.022. Epub 2011 Mar 13.

Authors

Fuu-Jen Tsai¹, Cheng-Wen Lin², Chien-Chen Lai³, Yu-Ching Lan⁴, Chih-Ho Lai⁵, Chien-Hui Hung⁶, Kai-Chung Hsueh⁷, Ting-Hsu Lin⁸, Hebron C Chang⁹, Lei Wan¹, Jim Jinn-Chyuan Sheu¹, Ying-Ju Lin¹⁰

Affiliations

¹ 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.
² Department of Biotechnology, Asia University, Taichung, Taiwan, ROC; Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan, ROC.
³ Institute of Molecular Biology, National Chung Hsing University, Taichung, Taiwan, ROC.
⁴ Department of Health Risk Management, China Medical University, Taichung, Taiwan, ROC.
⁵ Department of Microbiology, School of Medicine, China Medical University, Taichung, Taiwan, ROC.
⁶ Graduate Institute of Clinical Medical Science, Chang-Gung University, Chiayi, Taiwan, ROC.
⁷ Department of Pediatrics, Taichung Hospital Department of Health, Taichung, Taiwan, ROC.
⁸ Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, ROC.
⁹ Department of Biotechnology, Asia University, Taichung, Taiwan, ROC.
¹⁰ 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.

PMID: 25212137
DOI: 10.1016/j.foodchem.2011.03.022

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.

Keywords: Enterovirus 71; Internal ribosome entry site; Kaempferol; Trans-acting factors.