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Nat Biotechnol. 2015 May;33(5):549-554. doi: 10.1038/nbt.3179. Epub 2015 Mar 23.

Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody.

Author information

1
Institut National de la Santé et de la Recherche Médicale, U1110, Strasbourg, France.
2
Université de Strasbourg, Strasbourg, France.
3
Hepatitis C Research Group, Institute for Biomedical Research, University of Birmingham, Birmingham, United Kingdom.
4
Institut National de la Santé et de la Recherche Médicale, U913, Nantes, France.
5
Université de Nantes, Nantes, France.
6
Institut des Maladies de l'Appareil Digestif, CHU Nantes, Hôpital Hôtel-Dieu, Nantes, France.
7
Department of Biomedicine, Hepatology Laboratory, University of Basel, Basel, Switzerland.
8
I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
9
Architecture et Réactivité de l'ARN, Institut de Biologie Moléculaire et Cellulaire du CNRS - UPR 9002, Strasbourg, France.
10
Electron Microscopy Facility, Harvard Medical School, Boston, USA.
11
Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
12
German Centre for Infection Research, Heidelberg University, Heidelberg, Germany.
13
Pôle Hépato-Digestif, Institut Hopitalo-Universitaire, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
14
Center for Vaccinology, Ghent University, Ghent, Belgium.
15
Plateforme de Chimie Biologique Intégrative de Strasbourg, UMS 3286 CNRS-UdS & FMTS, Illkirch, France.
16
Institute for Medical Informatics and Biometry, Medical Faculty, Technische Universität Dresden, Dresden, Germany.
#
Contributed equally

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.

Comment in

PMID:
25798937
PMCID:
PMC4430301
DOI:
10.1038/nbt.3179
[Indexed for MEDLINE]
Free PMC Article

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