title: Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody.
abstract: Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and cancer. Cell entry of HCV and other pathogens is mediated by tight junction (TJ) proteins, but successful therapeutic targeting of TJ proteins has not been reported yet. Using a human liver-chimeric mouse model, we show that a monoclonal antibody specific for the TJ protein claudin-1 (ref. 7) eliminates chronic HCV infection without detectable toxicity. This antibody inhibits HCV entry, cell-cell transmission and virus-induced signaling events. Antibody treatment reduces the number of HCV-infected hepatocytes in vivo, highlighting the need for de novo infection by means of host entry factors to maintain chronic infection. In summary, we demonstrate that an antibody targeting a virus receptor can cure chronic viral infection and uncover TJ proteins as targets for antiviral therapy.
authors: Institut National de la Santé et de la Recherche Médicale, U1110, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors: Laurent
authors: L
authors: Mailly
authors: Institut National de la Santé et de la Recherche Médicale, U1110, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors: Fei
authors: F
authors: Xiao
authors: Institut National de la Santé et de la Recherche Médicale, U1110, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors: Joachim
authors: J
authors: Lupberger
authors: Hepatitis C Research Group, Institute for Biomedical Research, University of Birmingham, Birmingham, United Kingdom.
authors: Garrick K
authors: GK
authors: Wilson
authors: Institut National de la Santé et de la Recherche Médicale, U913, Nantes, France.|Université de Nantes, Nantes, France.|Institut des Maladies de l'Appareil Digestif, CHU Nantes, Hôpital Hôtel-Dieu, Nantes, France.
authors: Philippe
authors: P
authors: Aubert
authors: Department of Biomedicine, Hepatology Laboratory, University of Basel, Basel, Switzerland.
authors: François H T
authors: FHT
authors: Duong
authors: Department of Biomedicine, Hepatology Laboratory, University of Basel, Basel, Switzerland.
authors: Diego
authors: D
authors: Calabrese
authors: Institut National de la Santé et de la Recherche Médicale, U1110, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors: Céline
authors: C
authors: Leboeuf
authors: Institut National de la Santé et de la Recherche Médicale, U1110, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors: Isabel
authors: I
authors: Fofana
authors: Institut National de la Santé et de la Recherche Médicale, U1110, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors: Christine
authors: C
authors: Thumann
authors: Institut National de la Santé et de la Recherche Médicale, U1110, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors: Simonetta
authors: S
authors: Bandiera
authors: I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Marc
authors: M
authors: Lütgehetmann
authors: I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Tassilo
authors: T
authors: Volz
authors: Hepatitis C Research Group, Institute for Biomedical Research, University of Birmingham, Birmingham, United Kingdom.
authors: Christopher
authors: C
authors: Davis
authors: Hepatitis C Research Group, Institute for Biomedical Research, University of Birmingham, Birmingham, United Kingdom.
authors: Helen J
authors: HJ
authors: Harris
authors: Hepatitis C Research Group, Institute for Biomedical Research, University of Birmingham, Birmingham, United Kingdom.
authors: Christopher J
authors: CJ
authors: Mee
authors: Université de Strasbourg, Strasbourg, France.|Architecture et Réactivité de l'ARN, Institut de Biologie Moléculaire et Cellulaire du CNRS - UPR 9002, Strasbourg, France.
authors: Erika
authors: E
authors: Girardi
authors: Université de Strasbourg, Strasbourg, France.|Architecture et Réactivité de l'ARN, Institut de Biologie Moléculaire et Cellulaire du CNRS - UPR 9002, Strasbourg, France.
authors: Béatrice
authors: B
authors: Chane-Woon-Ming
authors: Electron Microscopy Facility, Harvard Medical School, Boston, USA.
authors: Maria
authors: M
authors: Ericsson
authors: Université de Nantes, Nantes, France.
authors: Nicola
authors: N
authors: Fletcher
authors: Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.|German Centre for Infection Research, Heidelberg University, Heidelberg, Germany.
authors: Ralf
authors: R
authors: Bartenschlager
authors: Institut National de la Santé et de la Recherche Médicale, U1110, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|Pôle Hépato-Digestif, Institut Hopitalo-Universitaire, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors: Patrick
authors: P
authors: Pessaux
authors: Center for Vaccinology, Ghent University, Ghent, Belgium.
authors: Koen
authors: K
authors: Vercauteren
authors: Center for Vaccinology, Ghent University, Ghent, Belgium.
authors: Philip
authors: P
authors: Meuleman
authors: Université de Strasbourg, Strasbourg, France.|Plateforme de Chimie Biologique Intégrative de Strasbourg, UMS 3286 CNRS-UdS & FMTS, Illkirch, France.
authors: Pascal
authors: P
authors: Villa
authors: Institute for Medical Informatics and Biometry, Medical Faculty, Technische Universität Dresden, Dresden, Germany.
authors: Lars
authors: L
authors: Kaderali
authors: Université de Strasbourg, Strasbourg, France.|Architecture et Réactivité de l'ARN, Institut de Biologie Moléculaire et Cellulaire du CNRS - UPR 9002, Strasbourg, France.
authors: Sébastien
authors: S
authors: Pfeffer
authors: Department of Biomedicine, Hepatology Laboratory, University of Basel, Basel, Switzerland.
authors: Markus H
authors: MH
authors: Heim
authors: Institut National de la Santé et de la Recherche Médicale, U913, Nantes, France.|Université de Nantes, Nantes, France.|Institut des Maladies de l'Appareil Digestif, CHU Nantes, Hôpital Hôtel-Dieu, Nantes, France.
authors: Michel
authors: M
authors: Neunlist
authors: Institut National de la Santé et de la Recherche Médicale, U1110, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors: Mirjam B
authors: MB
authors: Zeisel
authors: I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Maura
authors: M
authors: Dandri
authors: Hepatitis C Research Group, Institute for Biomedical Research, University of Birmingham, Birmingham, United Kingdom.
authors: Jane A
authors: JA
authors: McKeating
authors: Institut National de la Santé et de la Recherche Médicale, U1110, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors: Eric
authors: E
authors: Robinet
authors: Institut National de la Santé et de la Recherche Médicale, U1110, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|Pôle Hépato-Digestif, Institut Hopitalo-Universitaire, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors: Thomas F
authors: TF
authors: Baumert
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000276:immunology; D062445:Claudin-1 / Q000276:immunology* / Q000627:therapeutic use; D016174:Hepacivirus / Q000276:immunology / Q000472:pathogenicity; D006526:Hepatitis C / Q000276:immunology / Q000628:therapy* / Q000821:virology; D022781:Hepatocytes / Q000276:immunology; D006801:Humans; D008103:Liver Cirrhosis / Q000276:immunology* / Q000628:therapy / Q000821:virology; D051379:Mice
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D062445:Claudin-1