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

Research output: Contribution to journalArticle

Authors

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

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)549-554
Number of pages6
JournalNature Biotechnology
Volume33
Issue number5
Early online date23 Mar 2015
Publication statusPublished - May 2015

Keywords

  • Hepatitis C virus