Clearance of Persistent Hepatitis C Virus Infection in Humanized Mice Using a claudin-1-targeting Monoclonal Antibody

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / immunology
  • Claudin-1 / immunology*
  • Claudin-1 / therapeutic use
  • Hepacivirus / immunology
  • Hepacivirus / pathogenicity
  • Hepatitis C / immunology
  • Hepatitis C / therapy*
  • Hepatitis C / virology
  • Hepatocytes / immunology
  • Humans
  • Liver Cirrhosis / immunology*
  • Liver Cirrhosis / therapy
  • Liver Cirrhosis / virology
  • Mice

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Claudin-1