EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy. - Archive ouverte HAL Access content directly
Journal Articles Nature Medicine Year : 2011

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

(1) , (1) , (1) , (1) , (1) , (1) , (2) , (2) , (1) , (1, 3) , (1) , (4) , (1) , (5) , (5) , (5) , (6) , (7) , (8) , (9) , (1, 9) , (4) , (4) , (2) , (4) , (1, 9)
1
2
3
4
5
6
7
8
9
Cosset François-Loïc
Thomas Pietschmann

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.
Fichier principal
Vignette du fichier
BAUMERT_NMED-A48841B.pdf (513.04 Ko) Télécharger le fichier
Vignette du fichier
BAUMERT_NMED-A48841B_Supplement.doc (5.42 Mo) Télécharger le fichier
Vignette du fichier
Figures_1-_6_main_MS_02-03-11.pdf (2.5 Mo) Télécharger le fichier
Vignette du fichier
inserm-00705829_edited.pdf (701.33 Ko) Télécharger le fichier
Vignette du fichier
supplementary_table1.xls (203.5 Ko) Télécharger le fichier
Vignette du fichier
supplementary_table2.xls (45.5 Ko) Télécharger le fichier
Origin : Files produced by the author(s)
Format : Other
Origin : Files produced by the author(s)
Origin : Files produced by the author(s)
Format : Other
Format : Other
Loading...

Dates and versions

inserm-00705829 , version 1 (24-10-2012)

Identifiers

Cite

Joachim Lupberger, Mirjam B. 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, 2011, 17 (5), pp.589-95. ⟨10.1038/nm.2341⟩. ⟨inserm-00705829⟩
507 View
1428 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More