Single Particle Imaging of Polarized Hepatoma Organoids upon Hepatitis C Virus Infection Reveals an Ordered and Sequential Entry Process

Publication date: 14 March 2018
Source:Cell Host & Microbe, Volume 23, Issue 3
Author(s): Yasmine Baktash, Anisha Madhav, Kelly E. Coller, Glenn Randall
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.

Graphical abstract

Teaser

HCV entry is complex and involves multiple host factors. By imaging the infection of polarized hepatoma organoids with fluorescent HCV virions, Baktash et al. define the sequence of events during entry. They determine that HCV virions traffic with early receptors to tight junctions and then internalize in an EGFR-dependent manner.


http://ift.tt/2HzApYP