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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Main Authors: Jean Agnetti, Christophe Desterke, Ama Gassama-Diagne
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:Pathogens
Subjects:
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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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