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SCIENCE ADVANCES | RESEARCH ARTICLE VIROLOGY Copyright © 2020 The Authors, some rights reserved; Liver-expressed Cd302 and Cr1l limit hepatitis C virus exclusive licensee American Association cross-species transmission to mice for the Advancement Richard J. P. Brown1,2*, Birthe Tegtmeyer2, Julie Sheldon2, Tanvi Khera2,3, Anggakusuma2,4, of Science. No claim to 2,5,6 2,7 2 2 2 original U.S. Government Daniel Todt , Gabrielle Vieyres , Romy Weller , Sebastian Joecks , Yudi Zhang , Works. Distributed 2 2 2 2 2,5 Svenja Sake , Dorothea Bankwitz , Kathrin Welsch , Corinne Ginkel , Michael Engelmann , under a Creative 8,9 2,5 10,11 10,11 Gisa Gerold , Eike Steinmann , Qinggong Yuan , Michael Ott , Commons Attribution Florian W. R. Vondran12,13, Thomas Krey13,14,15,16,17, Luisa J. Ströh14, Csaba Miskey18, NonCommercial Zoltán Ivics18, Vanessa Herder19, Wolfgang Baumgärtner19, Chris Lauber2,20, Michael Seifert20, License 4.0 (CC BY-NC). Alexander W. Tarr21,22, C. Patrick McClure21,22, Glenn Randall23, Yasmine Baktash24, Alexander Ploss25, Viet Loan Dao Thi26,27, Eleftherios Michailidis27, Mohsan Saeed26,28, Lieven Verhoye29, Philip Meuleman29, Natascha Goedecke30, Dagmar Wirth30,31, Charles M. Rice26, Thomas Pietschmann2,13,15* Downloaded from Hepatitis 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 http://advances.sciencemag.org/ the murine orthologs and their human counterparts.
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