Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

The matrix metalloproteinase ADAM10 supports hepatitis C virus entry and cell-to-cell spread via its sheddase activity

[thumbnail of Original Article]
Preview
PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
2MB
[thumbnail of Supporting Information] Other (Supporting Information)
981kB

Item Type:Article
Title:The matrix metalloproteinase ADAM10 supports hepatitis C virus entry and cell-to-cell spread via its sheddase activity
Creators Name:Carriquí-Madroñal, B., Sheldon, J., Duven, M., Stegmann, C., Cirksena, K., Wyler, E., Zapatero-Belinchón, F.J., Vondran, F.W.R. and Gerold, G.
Abstract:Hepatitis C virus (HCV) exploits the four entry factors CD81, scavenger receptor class B type I (SR-BI, also known as SCARB1), occludin, and claudin-1 as well as the co-factor epidermal growth factor receptor (EGFR) to infect human hepatocytes. Here, we report that the disintegrin and matrix metalloproteinase 10 (ADAM10) associates with CD81, SR-BI, and EGFR and acts as HCV host factor. Pharmacological inhibition, siRNA-mediated silencing and genetic ablation of ADAM10 reduced HCV infection. ADAM10 was dispensable for HCV replication but supported HCV entry and cell-to-cell spread. Substrates of the ADAM10 sheddase including epidermal growth factor (EGF) and E-cadherin, which activate EGFR family members, rescued HCV infection of ADAM10 knockout cells. ADAM10 did not influence infection with other enveloped RNA viruses such as alphaviruses and a common cold coronavirus. Collectively, our study reveals a critical role for the sheddase ADAM10 as a HCV host factor, contributing to EGFR family member transactivation and as a consequence to HCV uptake.
Keywords:Hepatitis C Virus, Flow Cytometry, Small Interfering RNA, Luciferase, Hepatocytes, Hepatoma Cells, Cell Staining, Metalloproteases
Source:PLoS Pathogens
ISSN:1553-7366
Publisher:Public Library of Science
Volume:19
Number:11
Page Range:e1011759
Date:15 November 2023
Official Publication:https://doi.org/10.1371/journal.ppat.1011759
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library