PI3K/SHIP2/PTEN pathway in cell polarity and hepatitis C virus pathogenesis

作     者：Aline Awad Ama Gassama-Diagne 

作者机构：Inserm Unite 1193Hopital Paul Brousse Univ Paris-SudUMR-S 1193Univsite Paris-Saclay 

出 版 物：《World Journal of Hepatology》 (世界肝病学杂志（英文版）（电子版）)

年 卷 期：2017年第9卷第1期

页      面：18-29页

学科分类：1004[医学-公共卫生与预防医学(可授医学、理学学位)] 100401[医学-流行病与卫生统计学] 10[医学] 

基　　金：Supported by Agence Nationale de Recherche sur le Sida et les hépatites(ANRS France) Ligue contre le cancer France 

主　　题：Hepatitis C virus Phosphoinositide 3-kinase SH2-containing inositol polyphosphate 5-phosphatase Epithelial cell polarity Phosphoinositides 

摘      要：Hepatitis C virus(HCV) infects hepatocytes, polarized cells in the liver. Chronic HCV infection often leads to steatosis, fibrosis, cirrhosis and hepatocellular carcinoma, and it has been identified as the leading cause of liver transplantation worldwide. The HCV replication cycle is dependent on lipid metabolism and particularly an accumulation of lipid droplets in host cells. Phosphoinositides(PIs) are minor phospholipids enriched in different membranes and their levels are tightly regulated by specific PI kinases and phosphatases. PIs are implicated in a vast array of cellular responses that are central to morphogenesis, such as cytoskeletal changes, cytokinesis and the recruitment of downstream effectors to govern mechanisms involved in polarization and lumen formation. Important reviews of the literature identified phosphatidylinositol(Ptd Ins) 4-kinases, and their lipid products Ptd Ins(4)P, as critical regulators of the HCV life cycle. SH2-containing inositol polyphosphate 5-phosphatase(SHIP2), phosphoinositide 3-kinase(PI3K) and their lipid products Ptd Ins(3,4)P2 and Ptd Ins(3,4,5)P3, respectively, play an important role in the cell membrane and are key to the establishment of apicobasal polarity and lumen formation. In this review, we will focus on these new functions of PI3 K and SHIP2, and their deregulation by HCV, causing a disruption of apicobasal polarity, actin organization and extracellular matrix assembly. Finally we will highlight the involvement of this pathway in the event of insulin resistance and nonalcoholic fatty liver disease related to HCV infection.