Asunaprevir Evokes Hepatocytes Innate Immunity to Restrict the Replication of Hepatitis C and Dengue Virus

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Asunaprevir Evokes Hepatocytes Innate Immunity to Restrict the Replication of Hepatitis C and Dengue Virus

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dc.contributor.author Tsai, Wei-Lun en_US
dc.contributor.author Cheng, Jin-Shiung en_US
dc.contributor.author Shu, Chih-Wen en_US
dc.contributor.author Lai, Kwok-Hung en_US
dc.contributor.author Chan, Hoi-Hung en_US
dc.contributor.author Wu, Chun-Ching en_US
dc.contributor.author Wu, Jing-Mei en_US
dc.contributor.author Hsu, Ping-I en_US
dc.contributor.author Chung, Raymond T. en_US
dc.contributor.author Chang, Tsung-Hsien en_US
dc.date.accessioned 2017-06-15T18:29:01Z
dc.date.issued 2017 en_US
dc.identifier.citation Tsai, Wei-Lun, Jin-Shiung Cheng, Chih-Wen Shu, Kwok-Hung Lai, Hoi-Hung Chan, Chun-Ching Wu, Jing-Mei Wu, Ping-I Hsu, Raymond T. Chung, and Tsung-Hsien Chang. 2017. “Asunaprevir Evokes Hepatocytes Innate Immunity to Restrict the Replication of Hepatitis C and Dengue Virus.” Frontiers in Microbiology 8 (1): 668. doi:10.3389/fmicb.2017.00668. http://dx.doi.org/10.3389/fmicb.2017.00668. en
dc.identifier.issn en
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:33029729
dc.description.abstract Type I Interferon-mediated innate immunity against Flaviviridae, such as Hepatitis C virus (HCV) and Dengue virus (DENV), involves TLR3, RIG-I-like receptor (RLR) and JAK-STAT signal pathways. Asunaprevir is a newly developed HCV protease inhibitor for HCV treatment. Whether, asunaprevir activates innate immunity to restrict viral infection is unclear. Thus, this study investigates the effect of asunaprevir on innate immunity and its influence on HCV and DENV infection. Huh 7.5.1, Hep-G2 cells, JFH-1 infection model, and DENV-2 infection were used for the analysis. The activity of asunaprevir-regulated innate immunity signal pathway was assessed with IFN-β promoter or IFN-stimulated responsive element (ISRE) reporter assays and immunoblotting of key signal proteins. siRNA-mediated MAVS and TRIF knockdown of cells was performed to assess the effect of asunaprevir-regulated innate immunity against HCV and DENV. Asunaprevir treatment activated ISRE and IFN-β promoter-luciferase activities and signaling proteins in the JAK-STAT, MAVS, and TRIF pathways in Huh 7.5.1 cells. Asunaprevir-mediated signaling activation was decreased in MAVS-knockdown cells. Importantly, both RNA and protein levels of DENV-2 NS3 were decreased in asunaprevir-treated Huh 7.5.1 and HepG2 cells. In MAVS-knockdown cells, the restrictive effect of asunaprevir on HCV and DENV was attenuated. Our findings reveal an unexpected activity of asunaprevir, the activation of MAVS dependent innate immunity to restrict HCV and DENV infection. en
dc.language.iso en_US en
dc.publisher Frontiers Media S.A. en
dc.relation.isversionof doi:10.3389/fmicb.2017.00668 en
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5397474/pdf/ en
dash.license LAA en_US
dc.subject hepatitis C en
dc.subject Dengue virus en
dc.subject innate immunity en
dc.subject interferon type I en
dc.subject asunaprevir en
dc.title Asunaprevir Evokes Hepatocytes Innate Immunity to Restrict the Replication of Hepatitis C and Dengue Virus en
dc.type Journal Article en_US
dc.description.version Version of Record en
dc.relation.journal Frontiers in Microbiology en
dc.date.available 2017-06-15T18:29:01Z

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