%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 }