Roles of epidermal growth factor receptor, claudin-1 and occludin in multi-step entry of hepatitis C virus into polarized hepatoma spheroids.
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 singl...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-12-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1011887 |
| _version_ | 1797315933945987072 |
|---|---|
| author | Chui-Wa So Marion Sourisseau Shamila Sarwar Matthew J Evans Glenn Randall |
| author_facet | Chui-Wa So Marion Sourisseau Shamila Sarwar Matthew J Evans Glenn Randall |
| author_sort | Chui-Wa So |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T03:11:03Z |
| format | Article |
| id | doaj.art-b2235c81917e4912be99937de06fc0ef |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-03-08T03:11:03Z |
| publishDate | 2023-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-b2235c81917e4912be99937de06fc0ef2024-02-13T05:32:24ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-12-011912e101188710.1371/journal.ppat.1011887Roles of epidermal growth factor receptor, claudin-1 and occludin in multi-step entry of hepatitis C virus into polarized hepatoma spheroids.Chui-Wa SoMarion SourisseauShamila SarwarMatthew J EvansGlenn RandallThe 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.https://doi.org/10.1371/journal.ppat.1011887 |
| spellingShingle | Chui-Wa So Marion Sourisseau Shamila Sarwar Matthew J Evans Glenn Randall Roles of epidermal growth factor receptor, claudin-1 and occludin in multi-step entry of hepatitis C virus into polarized hepatoma spheroids. PLoS Pathogens |
| title | Roles of epidermal growth factor receptor, claudin-1 and occludin in multi-step entry of hepatitis C virus into polarized hepatoma spheroids. |
| title_full | Roles of epidermal growth factor receptor, claudin-1 and occludin in multi-step entry of hepatitis C virus into polarized hepatoma spheroids. |
| title_fullStr | Roles of epidermal growth factor receptor, claudin-1 and occludin in multi-step entry of hepatitis C virus into polarized hepatoma spheroids. |
| title_full_unstemmed | Roles of epidermal growth factor receptor, claudin-1 and occludin in multi-step entry of hepatitis C virus into polarized hepatoma spheroids. |
| title_short | Roles of epidermal growth factor receptor, claudin-1 and occludin in multi-step entry of hepatitis C virus into polarized hepatoma spheroids. |
| title_sort | roles of epidermal growth factor receptor claudin 1 and occludin in multi step entry of hepatitis c virus into polarized hepatoma spheroids |
| url | https://doi.org/10.1371/journal.ppat.1011887 |
| work_keys_str_mv | AT chuiwaso rolesofepidermalgrowthfactorreceptorclaudin1andoccludininmultistepentryofhepatitiscvirusintopolarizedhepatomaspheroids AT marionsourisseau rolesofepidermalgrowthfactorreceptorclaudin1andoccludininmultistepentryofhepatitiscvirusintopolarizedhepatomaspheroids AT shamilasarwar rolesofepidermalgrowthfactorreceptorclaudin1andoccludininmultistepentryofhepatitiscvirusintopolarizedhepatomaspheroids AT matthewjevans rolesofepidermalgrowthfactorreceptorclaudin1andoccludininmultistepentryofhepatitiscvirusintopolarizedhepatomaspheroids AT glennrandall rolesofepidermalgrowthfactorreceptorclaudin1andoccludininmultistepentryofhepatitiscvirusintopolarizedhepatomaspheroids |