{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T05:26:46Z","timestamp":1791869206412,"version":"4.3.4"},"reference-count":48,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T00:00:00Z","timestamp":1623888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2017R1A2B2002289"],"award-info":[{"award-number":["NRF-2017R1A2B2002289"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1A6A1A030525124"],"award-info":[{"award-number":["2018R1A6A1A030525124"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hepatitis C virus (HCV) is associated with various liver diseases. Chronic HCV infection is characterized by an abnormal host immune response. Therefore, it is speculated that to suppress HCV, a well-regulated host immune response is necessary. 2-O-methylhonokiol was identified by the screening of anti-HCV compounds using Renilla luciferase assay in Huh 7.5\/Con 1 genotype 1b replicon cells. Here, we investigated the mechanism by which 2-O-methylhonokiol treatment inhibits HCV replication using real-time PCR. Our data shows that treatment with 2-O-methylhonokiol activated innate immune responses via nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway. Additionally, the immunoprecipitation result shows that treatment with 2-O-methylhonokiol augmented tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) by preventing p62 from binding to TRAF6, resulting in reduced autophagy caused by HCV. Finally, we reproduced our data with the conditioned media from 2-O-methylhonokiol-treated cells. These findings strongly suggest that 2-O-methylhonokiol enhances the host immune response and suppresses HCV replication via TRAF6-mediated NF-kB activation.<\/jats:p>","DOI":"10.3390\/ijms22126499","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T11:20:26Z","timestamp":1623928826000},"page":"6499","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["2-O-Methylhonokiol Suppresses HCV Replication via TRAF6-Mediated NF-kB Activation"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7538-880X","authenticated-orcid":false,"given":"Suyun","family":"Jeong","sequence":"first","affiliation":[{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9560-5640","authenticated-orcid":false,"given":"Young-seok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-su","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungsoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea"},{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joohun","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea"},{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7117-1008","authenticated-orcid":false,"given":"Insug","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea"},{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5764-9482","authenticated-orcid":false,"given":"Wonchae","family":"Choe","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea"},{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1055\/s-2000-9505","article-title":"Recovery, persistence, and sequelae in hepatitis C virus infection: A perspective on long-term outcome","volume":"20","author":"Alter","year":"2000","journal-title":"Semin. 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