%0 Journal Article
%1 10.1371/journal.ppat.1011759
%A Carriquí-Madroñal, B
%A Sheldon, J
%A Duven, M
%A Stegmann, C
%A Cirksena, K
%A Wyler, E
%A Zapatero-Belinchón, F J
%A Vondran, Florian W R
%A Gerold, G
%D 2023
%I Public Library of Science
%J PLoS Pathog
%K pietschmann
%N 11
%P 1-24
%R 10.1371/journal.ppat.1011759
%T The matrix metalloproteinase ADAM10 supports hepatitis C virus entry and cell-to-cell spread via its sheddase activity
%U https://pubmed.ncbi.nlm.nih.gov/37967063/
%V 19
%X 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.