@article{3981,
  keywords = {Animals, Mice, Mice, Transgenic, Hepacivirus, Hepatitis C, Virus Internalization},
  author = {Richard Brown and Birthe Tegtmeyer and Julie Sheldon and Tanvi Khera and Daniel Todt and Gabrielle Vieyres and Romy Weller and Sebastian Joecks and Yudi Zhang and Svenja Sake and Dorothea Bankwitz and Kathrin Welsch and Corinne Ginkel and Michael Engelmann and Gisa Gerold and Eike Steinmann and Qinggong Yuan and Michael Ott and Florian Vondran and Thomas Krey and Luisa Str{\"o}h and Csaba Miskey and Zolt{\'a}n Ivics and Vanessa Herder and Wolfgang Baumg{\"a}rtner and Chris Lauber and Michael Seifert and Alexander Tarr and C Patrick McClure and Glenn Randall and Yasmine Baktash and Alexander Ploss and Viet Thi and Eleftherios Michailidis and Mohsan Saeed and Lieven Verhoye and Philip Meuleman and Natascha Goedecke and Dagmar Wirth and Charles Rice and Thomas Pietschmann},
  title = {Liver-expressed  and  limit hepatitis C virus cross-species transmission to mice.},
  abstract = { <p>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 the murine orthologs and their human counterparts. Genetic ablation of endogenous  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.</p> },
  year = {2020},
  journal = {Sci Adv},
  volume = {6},
  month = {2020 Nov},
  issn = {2375-2548},
  doi = {10.1126/sciadv.abd3233},
  language = {eng},
}