Mutations that alter use of hepatitis C virus cell entry factors mediate escape from neutralizing antibodies.

Abstract : BACKGROUND & AIMS: The development of vaccines and other strategies to prevent hepatitis C virus (HCV) infection is limited by rapid viral evasion. HCV entry is the first step of infection; this process involves several viral and host factors and is targeted by host-neutralizing responses. Although the roles of host factors in HCV entry have been well characterized, their involvement in evasion of immune responses is poorly understood. We used acute infection of liver graft as a model to investigate the molecular mechanisms of viral evasion. METHODS: We studied factors that contribute to evasion of host immune responses using patient-derived antibodies, HCV pseudoparticles, and cell culture-derived HCV that express viral envelopes from patients who have undergone liver transplantation. These viruses were used to infect hepatoma cell lines that express different levels of HCV entry factors. RESULTS: By using reverse genetic analyses, we identified altered use of host-cell entry factors as a mechanism by which HCV evades host immune responses. Mutations that alter use of the CD81 receptor also allowed the virus to escape neutralizing antibodies. Kinetic studies showed that these mutations affect virus-antibody interactions during postbinding steps of the HCV entry process. Functional studies with a large panel of patient-derived antibodies showed that this mechanism mediates viral escape, leading to persistent infection in general. CONCLUSIONS: We identified a mechanism by which HCV evades host immune responses, in which use of cell entry factors evolves with escape from neutralizing antibodies. These findings advance our understanding of the pathogenesis of HCV infection and might be used to develop antiviral strategies and vaccines.
Type de document :
Article dans une revue
Gastroenterology, WB Saunders, 2012, 143 (1), pp.223-233.e9. 〈10.1053/j.gastro.2012.04.006〉
Liste complète des métadonnées

Littérature citée [11 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00701511
Contributeur : Mirjam Zeisel <>
Soumis le : vendredi 25 mai 2012 - 15:16:06
Dernière modification le : dimanche 22 avril 2018 - 17:28:02
Document(s) archivé(s) le : jeudi 15 décembre 2016 - 09:04:22

Fichier

GASTRO-D-11-01111.R2_HAL.pdf
Fichiers produits par l'(les) auteur(s)

Identifiants

Collections

Citation

Isabel Fofana, Samira Fafi-Kremer, Patric Carolla, Catherine Fauvelle, Muhammad Nauman Zahid, et al.. Mutations that alter use of hepatitis C virus cell entry factors mediate escape from neutralizing antibodies.. Gastroenterology, WB Saunders, 2012, 143 (1), pp.223-233.e9. 〈10.1053/j.gastro.2012.04.006〉. 〈inserm-00701511〉

Partager

Métriques

Consultations de la notice

639

Téléchargements de fichiers

467