Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody
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Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody. / Mailly, Laurent; Xiao, Fei; Lupberger, Joachim; Wilson, Garrick K; Aubert, Philippe; Duong, François H T; Calabrese, Diego; Leboeuf, Céline; Fofana, Isabel; Thumann, Christine; Bandiera, Simonetta; Lütgehetmann, Marc; Volz, Tassilo; Davis, Christopher; Harris, Helen J; Mee, Christopher J; Girardi, Erika; Chane-Woon-Ming, Béatrice; Ericsson, Maria; Fletcher, Nicola; Bartenschlager, Ralf; Pessaux, Patrick; Vercauteren, Koen; Meuleman, Philip; Villa, Pascal; Kaderali, Lars; Pfeffer, Sébastien; Heim, Markus H; Neunlist, Michel; Zeisel, Mirjam B; Dandri-Petersen, Maura; McKeating, Jane A; Robinet, Eric; Baumert, Thomas F.
In: NAT BIOTECHNOL, Vol. 33, No. 5, 05.2015, p. 549-54.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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-Petersen, 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.
U2 - 10.1038/nbt.3179
DO - 10.1038/nbt.3179
M3 - SCORING: Journal article
C2 - 25798937
VL - 33
SP - 549
EP - 554
JO - NAT BIOTECHNOL
JF - NAT BIOTECHNOL
SN - 1087-0156
IS - 5
ER -