title: PI3K/SHIP2/PTEN pathway in cell polarity and hepatitis C virus pathogenesis.
abstract: 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 (PtdIns) 4-kinases, and their lipid products PtdIns(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 PtdIns(3,4)P2 and PtdIns(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 PI3K 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.
authors.affiliation: Aline Awad, Ama Gassama-Diagne, Inserm Unité 1193, Hôpital Paul Brousse, 94800 Villejuif, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Awad
authors.affiliation: Aline Awad, Ama Gassama-Diagne, Inserm Unité 1193, Hôpital Paul Brousse, 94800 Villejuif, France.
authors.forename: Ama
authors.initials: A
authors.lastname: Gassama-Diagne
keywords: Epithelial cell polarity; Hepatitis C virus; Phosphoinositide 3-kinase; Phosphoinositides; SH2-containing inositol polyphosphate 5-phosphatase