Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation

Fafi-Kremer, S. et al. (2010) Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation. Journal of Experimental Medicine, 207(9), pp. 2019-2031. (doi:10.1084/jem.20090766) (PMID:20713596) (PMCID:PMC2931157)

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Abstract

End-stage liver disease caused by chronic hepatitis C virus (HCV) infection is a leading cause for liver transplantation (LT). Due to viral evasion from host immune responses and the absence of preventive antiviral strategies, reinfection of the graft is universal. The mechanisms by which the virus evades host immunity to reinfect the liver graft are unknown. In a longitudinal analysis of six HCV-infected patients undergoing LT, we demonstrate that HCV variants reinfecting the liver graft were characterized by efficient entry and poor neutralization by antibodies present in pretransplant serum compared with variants not detected after transplantation. Monoclonal antibodies directed against HCV envelope glycoproteins or a cellular entry factor efficiently cross-neutralized infection of human hepatocytes by patient-derived viral isolates that were resistant to autologous host-neutralizing responses. These findings provide significant insights into the molecular mechanisms of viral evasion during HCV reinfection and suggest that viral entry is a viable target for prevention of HCV reinfection of the liver graft.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Patel, Professor Arvind
Authors: Fafi-Kremer, S., Fofana, I., Soulier, E., Carolla, P., Meuleman, P., Leroux-Roels, G., Patel, A.H., Cosset, F.-L., Pessaux, P., Doffoel, M., Wolf, P., Stoll-Keller, F., and Baumert, T.F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Experimental Medicine
Publisher:Rockefeller University Press
ISSN:0022-1007
ISSN (Online):1540-9538
Copyright Holders:Copyright © 2010 The Authors
First Published:First published in Journal of Experimental Medicine 207(9):2019-2031
Publisher Policy:Reproduced under a Creative Commons License

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