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Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation
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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931157/ https://www.ncbi.nlm.nih.gov/pubmed/20713596 http://dx.doi.org/10.1084/jem.20090766 |
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author | Fafi-Kremer, Samira Fofana, Isabel Soulier, Eric Carolla, Patric Meuleman, Philip Leroux-Roels, Geert Patel, Arvind H. Cosset, François-Loïc Pessaux, Patrick Doffoël, Michel Wolf, Philippe Stoll-Keller, Françoise Baumert, Thomas F. |
author_facet | Fafi-Kremer, Samira Fofana, Isabel Soulier, Eric Carolla, Patric Meuleman, Philip Leroux-Roels, Geert Patel, Arvind H. Cosset, François-Loïc Pessaux, Patrick Doffoël, Michel Wolf, Philippe Stoll-Keller, Françoise Baumert, Thomas F. |
author_sort | Fafi-Kremer, Samira |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2931157 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-29311572011-02-28 Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation Fafi-Kremer, Samira Fofana, Isabel Soulier, Eric Carolla, Patric Meuleman, Philip Leroux-Roels, Geert Patel, Arvind H. Cosset, François-Loïc Pessaux, Patrick Doffoël, Michel Wolf, Philippe Stoll-Keller, Françoise Baumert, Thomas F. J Exp Med Article 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. The Rockefeller University Press 2010-08-30 /pmc/articles/PMC2931157/ /pubmed/20713596 http://dx.doi.org/10.1084/jem.20090766 Text en © 2010 Fafi-Kremer et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Fafi-Kremer, Samira Fofana, Isabel Soulier, Eric Carolla, Patric Meuleman, Philip Leroux-Roels, Geert Patel, Arvind H. Cosset, François-Loïc Pessaux, Patrick Doffoël, Michel Wolf, Philippe Stoll-Keller, Françoise Baumert, Thomas F. Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation |
title | Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation |
title_full | Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation |
title_fullStr | Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation |
title_full_unstemmed | Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation |
title_short | Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation |
title_sort | viral entry and escape from antibody-mediated neutralization influence hepatitis c virus reinfection in liver transplantation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931157/ https://www.ncbi.nlm.nih.gov/pubmed/20713596 http://dx.doi.org/10.1084/jem.20090766 |
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