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

Laurent Mailly, Fei Xiao, Joachim Lupberger, Garrick K Wilson, Philippe Aubert, François H T Duong, Diego Calabrese, Céline Leboeuf, Isabel Fofana, Christine Thumann, Simonetta Bandiera, Marc Lütgehetmann, Tassilo Volz, Christopher Davis, Helen J Harris, Christopher J Mee, Erika Girardi, Béatrice Chane-Woon-Ming, Maria Ericsson, Nicola FletcherRalf Bartenschlager, Patrick Pessaux, Koen Vercauteren, Philip Meuleman, Pascal Villa, Lars Kaderali, Sébastien Pfeffer, Markus H Heim, Michel Neunlist, Mirjam B Zeisel, Maura Dandri, Jane A McKeating, Eric Robinet, Thomas F Baumert

Research output: Contribution to journalA1: Web of Science-article

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.

Original languageEnglish
JournalNature Biotechnology
Volume33
Issue number5
Pages (from-to)549-554
Number of pages6
ISSN1087-0156
DOIs
Publication statusPublished - 2015

Keywords

  • Animals
  • Antibodies, Monoclonal/administration & dosage
  • Antibodies, Monoclonal, Humanized/administration & dosage
  • Claudin-1/immunology
  • Hepacivirus/immunology
  • Hepatitis C/immunology
  • Hepatocytes/immunology
  • Humans
  • Liver Cirrhosis/immunology
  • Mice

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