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dc.date.accessioned2021-01-04T14:04:20Z
dc.date.available2021-01-04T14:04:20Z
dc.date.issued2020-11-04
dc.identifier.citationSci Adv. 2020 Nov 4;6(45):eabd3233. doi: 10.1126/sciadv.abd3233.en_US
dc.identifier.pmid33148654
dc.identifier.doi10.1126/sciadv.abd3233
dc.identifier.urihttp://hdl.handle.net/10033/622659
dc.description.abstractHepatitis C virus (HCV) has no animal reservoir, infecting only humans. To investigate species barrier determinants limiting infection of rodents, murine liver complementary DNA library screening was performed, identifying transmembrane proteins Cd302 and Cr1l as potent restrictors of HCV propagation. Combined ectopic expression in human hepatoma cells impeded HCV uptake and cooperatively mediated transcriptional dysregulation of a noncanonical program of immunity genes. Murine hepatocyte expression of both factors was constitutive and not interferon inducible, while differences in liver expression and the ability to restrict HCV were observed between the murine orthologs and their human counterparts. Genetic ablation of endogenous Cd302 expression in human HCV entry factor transgenic mice increased hepatocyte permissiveness for an adapted HCV strain and dysregulated expression of metabolic process and host defense genes. These findings highlight human-mouse differences in liver-intrinsic antiviral immunity and facilitate the development of next-generation murine models for preclinical testing of HCV vaccine candidates. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.en_US
dc.description.sponsorshipH2020 European Research Councilen_US
dc.language.isoenen_US
dc.publisherAmerican Association for the Advancement of Science (AAAS)en_US
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/ 281473en_US
dc.rightsopenAccessen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleLiver-expressed Cd302 and Cr1l limit hepatitis C virus cross-species transmission to miceen_US
dc.typeArticleen_US
dc.identifier.eissn2375-2548
dc.identifier.journalScience Advancesen_US
dc.identifier.pii10.1126/sciadv.abd3233
dc.source.volume6
dc.source.issue45
dc.source.beginpageeabd3233
dc.source.journaltitleScience Advances


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