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.
%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.
@article{10.1371/journal.ppat.1011759,
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.},
added-at = {2023-12-06T17:12:25.000+0100},
author = {Carriquí-Madroñal, B and Sheldon, J and Duven, M and Stegmann, C and Cirksena, K and Wyler, E and Zapatero-Belinchón, F J and Vondran, Florian W R and Gerold, G},
biburl = {https://www.bibsonomy.org/bibtex/27cbb4e0a7ab9a7a926a5eeff0d98da9b/pietschmann},
doi = {10.1371/journal.ppat.1011759},
interhash = {defe0f37f603c17439afcf1a1b707b04},
intrahash = {7cbb4e0a7ab9a7a926a5eeff0d98da9b},
journal = {PLoS Pathog},
keywords = {pietschmann},
month = {11},
number = 11,
pages = {1-24},
publisher = {Public Library of Science},
timestamp = {2023-12-06T17:12:25.000+0100},
title = {The matrix metalloproteinase ADAM10 supports hepatitis C virus entry and cell-to-cell spread via its sheddase activity},
url = {https://pubmed.ncbi.nlm.nih.gov/37967063/},
volume = 19,
year = 2023
}