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

L. Mailly, F. Xiao, J. Lupberger, G.K. Wilson, P. Aubert, F.H.T. Duong, D. Calabrese, C. Leboeuf, I. Fofana, C. Thumann, S. Bandiera, M. Lütgehetmann, T. Volz, C. Davis, H.J. Harris, Christopher Mee, E. Girardi, B. Chane-Woon-Ming, M. Ericsson, N. FletcherR. Bartenschlager, P. Pessaux, K. Vercauteren, P. Meuleman, P. Villa, L. Kaderali, S. Pfeffer, M.H. Heim, M. Neunlist, M.B. Zeisel, M. Dandri, J.A. McKeating, E. Robinet, T.F. Baumert

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Abstract

Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and cancer1. Cell entry of HCV2 and other pathogens3, 4, 5 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 model6, 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
Pages (from-to)549-554
JournalNature Biotechnology
Volume33
Issue number5
Early online date23 Mar 2015
DOIs
Publication statusPublished - 1 May 2015

Keywords

  • Hepatitis C
  • monoclonal antibody
  • chronic viral infection
  • antiviral therapy

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    Mailly, L., Xiao, F., Lupberger, J., Wilson, G. K., Aubert, P., Duong, F. H. T., ... Baumert, T. F. (2015). Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody. Nature Biotechnology, 33(5), 549-554. https://doi.org/10.1038/nbt.3179