Impact of HCV Infection on Hepatocyte Polarity and Plasticity
The hepatitis C virus (HCV) is an oncogenic virus that alters the cell polarization machinery in order to enter the hepatocyte and replicate. While these alterations are relatively well defined, their consequences in the evolution of the disease remain poorly documented. Since 2012, HCV infection ca...
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MDPI AG
2022-03-01
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Online Access: | https://www.mdpi.com/2076-0817/11/3/337 |
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author | Jean Agnetti Christophe Desterke Ama Gassama-Diagne |
author_facet | Jean Agnetti Christophe Desterke Ama Gassama-Diagne |
author_sort | Jean Agnetti |
collection | DOAJ |
description | The hepatitis C virus (HCV) is an oncogenic virus that alters the cell polarization machinery in order to enter the hepatocyte and replicate. While these alterations are relatively well defined, their consequences in the evolution of the disease remain poorly documented. Since 2012, HCV infection can be effectively cured with the advent of direct acting antivirals (DAA). Nevertheless, patients cured of their HCV infection still have a high risk of developing hepatocellular carcinoma (HCC). Importantly, it has been shown that some of the deregulations induced by HCV are maintained despite a sustained virologic response (SVR), including the down-regulation of some hepatocyte functions such as bile acid metabolism, exemplifying cell dedifferentiation, and the up-regulation of the epithelial–mesenchymal transition (EMT). EMT is a process by which epithelial cells lose their differentiation and their specific polarity to acquire mesenchymal cell properties, including migration and extracellular matrix remodeling capabilities. Of note, epithelial cell polarity acts as a gatekeeper against EMT. Thus, it remains important to elucidate the mechanisms by which HCV alters polarity and promotes EMT that could participate in viral-induced hepatic carcinogenesis. In this review, we define the main steps involved in the polarization process of epithelial cells and recall the essential cellular actors involved. We also highlight the particularities of hepatocyte polarity, responsible for their unique morphology. We then focus on the alterations by HCV of epithelial cell polarity and the consequences of the transformation of hepatocytes involved in the carcinogenesis process. |
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format | Article |
id | doaj.art-b3d9883c616a4d789c05ce838360ae5e |
institution | Directory Open Access Journal |
issn | 2076-0817 |
language | English |
last_indexed | 2024-03-09T13:03:05Z |
publishDate | 2022-03-01 |
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series | Pathogens |
spelling | doaj.art-b3d9883c616a4d789c05ce838360ae5e2023-11-30T21:52:39ZengMDPI AGPathogens2076-08172022-03-0111333710.3390/pathogens11030337Impact of HCV Infection on Hepatocyte Polarity and PlasticityJean Agnetti0Christophe Desterke1Ama Gassama-Diagne2INSERM, UMR-S 1193, Université Paris-Sud, F-94800 Villejuif, FranceUFR Médecine-INSERM UMS33, Université Paris-Sud, F-94800 Villejuif, FranceINSERM, UMR-S 1193, Université Paris-Sud, F-94800 Villejuif, FranceThe hepatitis C virus (HCV) is an oncogenic virus that alters the cell polarization machinery in order to enter the hepatocyte and replicate. While these alterations are relatively well defined, their consequences in the evolution of the disease remain poorly documented. Since 2012, HCV infection can be effectively cured with the advent of direct acting antivirals (DAA). Nevertheless, patients cured of their HCV infection still have a high risk of developing hepatocellular carcinoma (HCC). Importantly, it has been shown that some of the deregulations induced by HCV are maintained despite a sustained virologic response (SVR), including the down-regulation of some hepatocyte functions such as bile acid metabolism, exemplifying cell dedifferentiation, and the up-regulation of the epithelial–mesenchymal transition (EMT). EMT is a process by which epithelial cells lose their differentiation and their specific polarity to acquire mesenchymal cell properties, including migration and extracellular matrix remodeling capabilities. Of note, epithelial cell polarity acts as a gatekeeper against EMT. Thus, it remains important to elucidate the mechanisms by which HCV alters polarity and promotes EMT that could participate in viral-induced hepatic carcinogenesis. In this review, we define the main steps involved in the polarization process of epithelial cells and recall the essential cellular actors involved. We also highlight the particularities of hepatocyte polarity, responsible for their unique morphology. We then focus on the alterations by HCV of epithelial cell polarity and the consequences of the transformation of hepatocytes involved in the carcinogenesis process.https://www.mdpi.com/2076-0817/11/3/337HCVhepatocytespolarityEMTcell junctionstraffic |
spellingShingle | Jean Agnetti Christophe Desterke Ama Gassama-Diagne Impact of HCV Infection on Hepatocyte Polarity and Plasticity Pathogens HCV hepatocytes polarity EMT cell junctions traffic |
title | Impact of HCV Infection on Hepatocyte Polarity and Plasticity |
title_full | Impact of HCV Infection on Hepatocyte Polarity and Plasticity |
title_fullStr | Impact of HCV Infection on Hepatocyte Polarity and Plasticity |
title_full_unstemmed | Impact of HCV Infection on Hepatocyte Polarity and Plasticity |
title_short | Impact of HCV Infection on Hepatocyte Polarity and Plasticity |
title_sort | impact of hcv infection on hepatocyte polarity and plasticity |
topic | HCV hepatocytes polarity EMT cell junctions traffic |
url | https://www.mdpi.com/2076-0817/11/3/337 |
work_keys_str_mv | AT jeanagnetti impactofhcvinfectiononhepatocytepolarityandplasticity AT christophedesterke impactofhcvinfectiononhepatocytepolarityandplasticity AT amagassamadiagne impactofhcvinfectiononhepatocytepolarityandplasticity |