2-O-Methylhonokiol Suppresses HCV Replication via TRAF6-Mediated NF-kB Activation |
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Authors: | Suyun Jeong Young-seok Lee Kiyoon Kim Ji-su Yoon Sungsoo Kim Joohun Ha Insug Kang Wonchae Choe |
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Affiliation: | 1.Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea; (S.J.); (Y.-s.L.); (J.-s.Y.); (S.K.); (J.H.); (I.K.);2.Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Korea; |
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Abstract: | 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. |
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Keywords: | 2-O-methylhonokiol hepatitis C virus nuclear factor kappa-light-chain-enhancer of activated B cells innate immune response |
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