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Roles of epidermal growth factor receptor, claudin-1 and occludin in multi-step entry of hepatitis C virus into polarized hepatoma spheroids.
So, Chui-Wa; Sourisseau, Marion; Sarwar, Shamila; Evans, Matthew J; Randall, Glenn.
Affiliation
  • So CW; Department of Microbiology, The University of Chicago, Chicago, Illinois, United States of America.
  • Sourisseau M; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
  • Sarwar S; Department of Microbiology, The University of Chicago, Chicago, Illinois, United States of America.
  • Evans MJ; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
  • Randall G; Department of Microbiology, The University of Chicago, Chicago, Illinois, United States of America.
PLoS Pathog ; 19(12): e1011887, 2023 Dec.
Article in En | MEDLINE | ID: mdl-38157366
ABSTRACT
The multi-step process of hepatitis C virus (HCV) entry is facilitated by various host factors, including epidermal growth factor receptor (EGFR) and the tight junction proteins claudin-1 (CLDN1) and occludin (OCLN), which are thought to function at later stages of the HCV entry process. Using single particle imaging of HCV infection of polarized hepatoma spheroids, we observed that EGFR performs multiple functions in HCV entry, both phosphorylation-dependent and -independent. We previously observed, and in this study confirmed, that EGFR is not required for HCV migration to the tight junction. EGFR is required for the recruitment of clathrin to HCV in a phosphorylation-independent manner. EGFR phosphorylation is required for virion internalization at a stage following the recruitment of clathrin. HCV entry activates the RAF-MEK-ERK signaling pathway downstream of EGFR phosphorylation. This signaling pathway regulates the sorting and maturation of internalized HCV into APPL1- and EEA1-associated early endosomes, which form the site of virion uncoating. The tight junction proteins, CLDN1 and OCLN, function at two distinct stages of HCV entry. Despite its appreciated function as a "late receptor" in HCV entry, CLDN1 is required for efficient HCV virion accumulation at the tight junction. Huh-7.5 cells lacking CLDN1 accumulate HCV virions primarily at the initial basolateral surface. OCLN is required for the late stages of virion internalization. This study produced further insight into the unusually complex HCV endocytic process.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hepatitis C / Hepacivirus / Claudin-1 / Liver Neoplasms Limits: Humans Language: En Journal: PLoS Pathog Year: 2023 Document type: Article Affiliation country: Estados Unidos Country of publication: Estados Unidos

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hepatitis C / Hepacivirus / Claudin-1 / Liver Neoplasms Limits: Humans Language: En Journal: PLoS Pathog Year: 2023 Document type: Article Affiliation country: Estados Unidos Country of publication: Estados Unidos