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

Mailly, Laurent and Xiao, Fei and Lupberger, Joachim and Wilson, Garrick K. and Aubert, Philippe and Duong, François H. T. and Calabrese, Diego and Leboeuf, Céline and Fofana, Isabel and Thumann, Christine and Bandiera, Simonetta and Lütgehetmann, Marc and Volz, Tassilo and Davis, Christopher and Harris, Helen J. and Mee, Christopher J. and Girardi, Erika and Chane-Woon-Ming, Béatrice and Ericsson, Maria and Fletcher, Nicola and Bartenschlager, Ralf and Pessaux, Patrick and Vercauteren, Koen and Meuleman, Philip and Villa, Pascal and Kaderali, Lars and Pfeffer, Sébastien and Heim, Markus H. and Neunlist, Michel and Zeisel, Mirjam B. and Dandri, Maura and McKeating, Jane A. and Robinet, Eric and Baumert, Thomas F.. (2015) Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody. Nature Biotechnology, 33 (5). pp. 549-554.

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Official URL: https://edoc.unibas.ch/61771/

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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.

Faculties and Departments:	03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Hepatology Laboratory (Heim)
UniBasel Contributors:	Calabrese, Diego and Heim, Markus H.
Item Type:	Article, refereed
Article Subtype:	Research Article
Publisher:	Nature Publishing Group
ISSN:	1087-0156
e-ISSN:	1546-1696
Note:	Publication type according to Uni Basel Research Database: Journal article
Related URLs:	Green Open Access
Identification Number:	doi: 10.1038/nbt.3179 pmid: 25798937
Last Modified:	06 Nov 2018 17:43
Deposited On:	22 Oct 2018 15:56

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