1. Single Particle Imaging of Polarized Hepatoma Organoids upon Hepatitis C Virus Infection Reveals an Ordered and Sequential Entry Process.
- Author
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Baktash Y, Madhav A, Coller KE, and Randall G
- Subjects
- Actins metabolism, Cell Culture Techniques methods, Cell Line, Cell Membrane metabolism, Cell Survival, Claudin-1 metabolism, Endocytosis physiology, ErbB Receptors metabolism, Hepacivirus pathogenicity, Host-Pathogen Interactions physiology, Humans, Occludin metabolism, Scavenger Receptors, Class B metabolism, Tetraspanin 28 metabolism, Tight Junctions metabolism, Viral Nonstructural Proteins metabolism, Carcinoma, Hepatocellular diagnostic imaging, Carcinoma, Hepatocellular virology, Hepacivirus physiology, Hepatitis C virology, Imaging, Three-Dimensional methods, Organoids diagnostic imaging, Organoids metabolism, Organoids virology, Virus Internalization
- Abstract
Hepatitis C virus (HCV) enters hepatocytes via various entry factors, including scavenger receptor BI (SR-B1), cluster of differentiation 81 (CD81), epidermal growth factor receptor (EGFR), claudin-1 (CLDN1), and occludin (OCLN). As CLDN1 and OCLN are not readily accessible due to their tight junctional localization, HCV likely accesses them by either disrupting cellular polarity or migrating to the tight junction. In this study, we image HCV entry into a three-dimensional polarized hepatoma system and reveal that the virus sequentially engages these entry factors through actin-dependent mechanisms. HCV initially localizes with the early entry factors SR-B1, CD81, and EGFR at the basolateral membrane and then accumulates at the tight junction in an actin-dependent manner. HCV associates with CLDN1 and then OCLN at the tight junction and is internalized via clathrin-mediated endocytosis by an active process requiring EGFR. Thus, HCV uses a dynamic and multi-step process to engage and enter host cells., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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