The matrix metalloproteinase ADAM10 supports hepatitis C virus entry and cell-to-cell spread via its sheddase activity.
Belén Carriquí-MadroñalJulie SheldonMara DuvenCora StegmannKarsten CirksenaEmanuel WylerFrancisco J Zapatero-BelinchónFlorian W R VondranGisa GeroldPublished in: PLoS pathogens (2023)
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.
Keyphrases
- hepatitis c virus
- epidermal growth factor receptor
- human immunodeficiency virus
- tyrosine kinase
- small cell lung cancer
- growth factor
- single cell
- cell therapy
- advanced non small cell lung cancer
- stem cells
- endothelial cells
- drug delivery
- genome wide
- dna methylation
- cell death
- binding protein
- liver injury
- cancer therapy
- induced pluripotent stem cells