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

Carriquí-Madroñal, B.; Sheldon, J.; Duven, M.; Stegmann, C.; Cirksena, K.; Wyler, E.; Zapatero-Belinchón, F.J.; Vondran, F.W.R.; Gerold, G.

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

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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

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