Hepatitis C Virus Increases Occludin Expression via the Upregulation of Adipose Differentiation-Related Protein

Branche, Emilie; Conzelmann, Stéphanie; Parisot, Clotilde; Bédert-Collins, Ludmila; Lévy, Pierre L; Bartosch, Birke; Clement, Sophie; Negro, Francesco

doi:10.1371/journal.pone.0146000

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Title		Hepatitis C Virus Increases Occludin Expression via the Upregulation of Adipose Differentiation-Related Protein
Authors		Branche, Emilie Conzelmann, Stéphanie Parisot, Clotilde Bédert-Collins, Ludmila Lévy, Pierre L Bartosch, Birke Clement, Sophie Negro, Francesco
Published in		PLOS ONE. 2016, vol. 11, no. 1, p. e0146000
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.
Identifiers		DOI: 10.1371/journal.pone.0146000 PMID: 26731658
Full text		Article (Published version) (1.9 MB) - Free access
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Research group		Etudes et traitement de l'hépatite C et B (554)
Citation (ISO format)		BRANCHE, Emilie et al. Hepatitis C Virus Increases Occludin Expression via the Upregulation of Adipose Differentiation-Related Protein. In: PLOS ONE, 2016, vol. 11, n° 1, p. e0146000. doi: 10.1371/journal.pone.0146000 https://archive-ouverte.unige.ch/unige:80800