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 Fletcher; Ralf 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

doi:10.1038/nbt.3179

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

Immunology and Immunotherapy

Research output: Contribution to journal › Article › peer-review

94 Citations (Scopus)

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 language	English
Pages (from-to)	549-554
Number of pages	6
Journal	Nature Biotechnology
Volume	33
Issue number	5
Early online date	23 Mar 2015
DOIs	https://doi.org/10.1038/nbt.3179
Publication status	Published - May 2015

Keywords

Hepatitis C virus

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/nbt.3179Licence: None: All rights reserved

The Role of Hepatitis C Virus Glycoprotein-Receptor Polymorphism in Viral Pathogenesis
McKeating, J.
Medical Research Council
1/01/12 → 30/06/17
Project: Research Councils
Mechanisms of Hepatitis C Virus Induced Hepatocyte Injury
McKeating, J. & Balfe, P.
Medical Research Council
1/10/09 → 30/09/12
Project: Research Councils

Cite this

Mailly, L., Xiao, F., Lupberger, J., Wilson, G. K., Aubert, P., Duong, F. H. T., Calabrese, D., Leboeuf, C., Fofana, I., Thumann, C., Bandiera, S., Lütgehetmann, M., Volz, T., Davis, C., Harris, H. J., Mee, C. J., Girardi, E., Chane-Woon-Ming, B., Ericsson, M., ... 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

@article{a4760e4b58c349cb85e0d2548337d777,

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

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.",

keywords = "Hepatitis C virus",

author = "Laurent Mailly and Fei Xiao and Joachim Lupberger and Wilson, {Garrick K} and Philippe Aubert and Duong, {Fran{\c c}ois H T} and Diego Calabrese and C{\'e}line Leboeuf and Isabel Fofana and Christine Thumann and Simonetta Bandiera and Marc L{\"u}tgehetmann and Tassilo Volz and Christopher Davis and Harris, {Helen J} and Mee, {Christopher J} and Erika Girardi and B{\'e}atrice Chane-Woon-Ming and Maria Ericsson and Nicola Fletcher and Ralf Bartenschlager and Patrick Pessaux and Koen Vercauteren and Philip Meuleman and Pascal Villa and Lars Kaderali and S{\'e}bastien Pfeffer and Heim, {Markus H} and Michel Neunlist and Zeisel, {Mirjam B} and Maura Dandri and McKeating, {Jane A} and Eric Robinet and Baumert, {Thomas F}",

year = "2015",

month = may,

doi = "10.1038/nbt.3179",

language = "English",

volume = "33",

pages = "549--554",

journal = "Nature Biotechnology",

issn = "1087-0156",

publisher = "Nature Publishing Group",

number = "5",

}

Mailly, L, Xiao, F, Lupberger, J, Wilson, GK, Aubert, P, Duong, FHT, Calabrese, D, Leboeuf, C, Fofana, I, Thumann, C, Bandiera, S, Lütgehetmann, M, Volz, T, Davis, C, Harris, HJ, Mee, CJ, Girardi, E, Chane-Woon-Ming, B, Ericsson, M, Fletcher, N, Bartenschlager, R, Pessaux, P, Vercauteren, K, Meuleman, P, Villa, P, Kaderali, L, Pfeffer, S, Heim, MH, Neunlist, M, Zeisel, MB, Dandri, M, McKeating, JA, Robinet, E & Baumert, TF 2015, 'Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody', Nature Biotechnology, vol. 33, no. 5, pp. 549-554. https://doi.org/10.1038/nbt.3179

TY - JOUR

T1 - Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody

AU - Mailly, Laurent

AU - Xiao, Fei

AU - Lupberger, Joachim

AU - Wilson, Garrick K

AU - Aubert, Philippe

AU - Duong, François H T

AU - Calabrese, Diego

AU - Leboeuf, Céline

AU - Fofana, Isabel

AU - Thumann, Christine

AU - Bandiera, Simonetta

AU - Lütgehetmann, Marc

AU - Volz, Tassilo

AU - Davis, Christopher

AU - Harris, Helen J

AU - Mee, Christopher J

AU - Girardi, Erika

AU - Chane-Woon-Ming, Béatrice

AU - Ericsson, Maria

AU - Fletcher, Nicola

AU - Bartenschlager, Ralf

AU - Pessaux, Patrick

AU - Vercauteren, Koen

AU - Meuleman, Philip

AU - Villa, Pascal

AU - Kaderali, Lars

AU - Pfeffer, Sébastien

AU - Heim, Markus H

AU - Neunlist, Michel

AU - Zeisel, Mirjam B

AU - Dandri, Maura

AU - McKeating, Jane A

AU - Robinet, Eric

AU - Baumert, Thomas F

PY - 2015/5

Y1 - 2015/5

N2 - 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.

AB - 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.

KW - Hepatitis C virus

U2 - 10.1038/nbt.3179

DO - 10.1038/nbt.3179

M3 - Article

C2 - 25798937

SN - 1087-0156

VL - 33

SP - 549

EP - 554

JO - Nature Biotechnology

JF - Nature Biotechnology

IS - 5

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Projects

The Role of Hepatitis C Virus Glycoprotein-Receptor Polymorphism in Viral Pathogenesis

Mechanisms of Hepatitis C Virus Induced Hepatocyte Injury

Cite this