title: Hepatitis C Virus Increases Occludin Expression via the Upregulation of Adipose Differentiation-Related Protein.
abstract: The hepatitis C virus (HCV) life cycle is closely associated with lipid metabolism. In particular, HCV assembly initiates at the surface of lipid droplets. To further understand the role of lipid droplets in HCV life cycle, we assessed the relationship between HCV and the adipose differentiation-related protein (ADRP), a lipid droplet-associated protein. Different steps of HCV life cycle were assessed in HCV-infected human Huh-7 hepatoma cells overexpressing ADRP upon transduction with a lentiviral vector. HCV infection increased ADRP mRNA and protein expression levels by 2- and 1.5-fold, respectively. The overexpression of ADRP led to an increase of (i) the surface of lipid droplets, (ii) the total cellular neutral lipid content (2.5- and 5-fold increase of triglycerides and cholesterol esters, respectively), (iii) the cellular free cholesterol level (5-fold) and (iv) the HCV particle production and infectivity (by 2- and 3.5-fold, respectively). The investigation of different steps of the HCV life cycle indicated that the ADRP overexpression, while not affecting the viral replication, promoted both virion egress and entry (~12-fold), the latter possibly via an increase of its receptor occludin. Moreover, HCV infection induces an increase of both ADRP and occludin expression. In HCV infected cells, the occludin upregulation was fully prevented by the ADRP silencing, suggesting a specific, ADRP-dependent mechanism. Finally, in HCV-infected human livers, occludin and ADRP mRNA expression levels correlated with each other. Alltogether, these findings show that HCV induces ADRP, which in turns appears to confer a favorable environment to viral spread.
authors.affiliation: Department of Immunology and Pathology, Faculty of Medicine, Geneva, Switzerland.
authors.forename: Emilie
authors.initials: E
authors.lastname: Branche
authors.affiliation: Department of Immunology and Pathology, Faculty of Medicine, Geneva, Switzerland.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Conzelmann
authors.affiliation: Department of Immunology and Pathology, Faculty of Medicine, Geneva, Switzerland.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Parisot
authors.affiliation: Department of Immunology and Pathology, Faculty of Medicine, Geneva, Switzerland.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Bedert
authors.affiliation: Department of Immunology and Pathology, Faculty of Medicine, Geneva, Switzerland.
authors.forename: Pierre L
authors.initials: PL
authors.lastname: Lévy
authors.affiliation: CRCL, INSERM U1052, CNRS 5286, University of Lyon, Lyon, France.
authors.forename: Birke
authors.initials: B
authors.lastname: Bartosch
authors.affiliation: Divisions of Clinical Pathology, University Hospital, Geneva, Switzerland.
authors.forename: Sophie
authors.initials: S
authors.lastname: Clément
authors.affiliation: Divisions of Clinical Pathology, University Hospital, Geneva, Switzerland.|Gastroenterology and Hepatology, University Hospital, Geneva, Switzerland.
authors.forename: Francesco
authors.initials: F
authors.lastname: Negro
mesh_terms: D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics* / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism / Q000821:virology; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism / Q000821:virology*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D062793:Occludin / Q000235:genetics* / Q000378:metabolism; D000070780:Perilipin-2; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation; D014779:Virus Replication
chemical_list: D008565:Membrane Proteins; D062793:Occludin; C000602982:PLIN2 protein, human; D000070780:Perilipin-2; D012333:RNA, Messenger