EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy.

Abstract : Hepatitis C virus (HCV) is a major cause of liver disease, but therapeutic options are limited and there are no prevention strategies. Viral entry is the first step of infection and requires the cooperative interaction of several host cell factors. Using a functional RNAi kinase screen, we identified epidermal growth factor receptor and ephrin receptor A2 as host cofactors for HCV entry. Blocking receptor kinase activity by approved inhibitors broadly impaired infection by all major HCV genotypes and viral escape variants in cell culture and in a human liver chimeric mouse model in vivo. The identified receptor tyrosine kinases (RTKs) mediate HCV entry by regulating CD81-claudin-1 co-receptor associations and viral glycoprotein-dependent membrane fusion. These results identify RTKs as previously unknown HCV entry cofactors and show that tyrosine kinase inhibitors have substantial antiviral activity. Inhibition of RTK function may constitute a new approach for prevention and treatment of HCV infection.
Type de document :
Article dans une revue
Nature Medicine, Nature Publishing Group, 2011, 17 (5), pp.589-95. 〈10.1038/nm.2341〉
Liste complète des métadonnées

Littérature citée [52 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00705829
Contributeur : Thomas Baumert <>
Soumis le : mercredi 24 octobre 2012 - 07:00:09
Dernière modification le : dimanche 22 avril 2018 - 17:28:02
Document(s) archivé(s) le : vendredi 25 janvier 2013 - 02:50:09

Identifiants

Collections

Citation

Joachim Lupberger, Mirjam Zeisel, Fei Xiao, Christine Thumann, Isabel Fofana, et al.. EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy.. Nature Medicine, Nature Publishing Group, 2011, 17 (5), pp.589-95. 〈10.1038/nm.2341〉. 〈inserm-00705829〉

Partager

Métriques

Consultations de la notice

670

Téléchargements de fichiers

1395