Hepatitis C virus infection inhibits P-body granule formation in human livers

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• dc.contributor.author Pérez Vilaró, Gemma, 1985-ca
• dc.contributor.author Fernández-Carrillo, Carlosca
• dc.contributor.author Mensa, Lauraca
• dc.contributor.author Miquel, Rosaca
• dc.contributor.author Sanjuan, Xavierca
• dc.contributor.author Forns, Xavierca
• dc.contributor.author Pérez del Pulgar, Sofíaca
• dc.contributor.author Díez Antón, Juana, 1962-ca
• dc.date.accessioned 2017-02-03T08:09:14Z
• dc.date.available 2017-02-03T08:09:14Z
• dc.date.issued 2015ca
• dc.description.abstract BACKGROUND & AIMS: Decoding the myriad of interactions that hepatitis C virus (HCV) establishes with infected cells is mandatory to obtain a complete understanding of HCV biology and its associated pathogenesis. We and others have previously found that HCV infection disrupts the formation of P-bodies in cell culture. These are cytoplasmic RNA granules with key roles in post-transcriptional regulation of gene expression. Therefore, P-body disruption might have consequences beyond viral propagation. However, whether P-body disruption occurs also in vivo is unknown. Aim of this study was to address this important issue. METHODS: Formalin-fixed paraffin-embedded liver biopsies from four groups of patients (healthy donors, patients with non-virus related liver inflammation, HCV- and HBV-infected patients) were immunostained to detect DDX6 and Dcp1, two core P-body components. Changes in the localization of these proteins were assessed by confocal microscopy. RESULTS: HCV specifically inhibited P-body formation in hepatocytes from human livers regardless of viral genotype, inflammation grade or whether the infection was recent or long established. Importantly, this alteration was reversed once HCV was eliminated by therapy. Furthermore, we observed in vivo an unexpected heterogeneity in P-body composition, which might reflect functional specializations. CONCLUSIONS: This is the first comprehensive in vivo P-body analysis that links a pathogenic condition to P-body alterations. Because of their role in gene expression, the alteration of P-bodies should be further studied to understand fully complex HCV-associated pathologies.
• dc.description.sponsorship JD and GPV were supported by a grant from the Spanish Ministry of Economy and Competitiveness (BFU2013-44629-R). XF received support in part by a grant from Instituto de Salud Carlos III (PI11/01907), Ministerio de Economía y Competitividad, cofunded by Fondo Europeo de Desarrollo Regional, Unión Europea, Una manera de hacer Europa. XF and SPP also received a grant/nfrom the Roche Organ Transplantation Research Foundation (ROTRF, CI: 442035057). The other authors were supported by grants from the following institutions: CFC from Asociación Española para el Estudio del Hígado, and LM from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad
• dc.format.mimetype application/pdfca
• dc.identifier.citation Pérez Vilaró G, Fernández-Carrillo C, Mensa L, Miquel R, Sanjuan X, Forns X, Pérez del Pulgar S, Díez Antón J. Hepatitis C virus infection inhibits P-body granule formation in human livers. J Hepatol. 2015 Apr; 62(4): 785-90. DOI: 10.1016/j.jhep.2014.11.018ca
• dc.identifier.doi http://dx.doi.org/10.1016/j.jhep.2014.11.018
• dc.identifier.issn 0168-8278ca
• dc.identifier.uri http://hdl.handle.net/10230/28043
• dc.language.iso engca
• dc.publisher Elsevierca
• dc.relation.ispartof Journal of Hepatology. 2015 Apr;62(4):785-90
• dc.rights © Elsevier http://dx.doi.org/10.1016/j.jhep.2014.11.018ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.subject.other Virus de l'hepatitis C
• dc.subject.other Fetge
• dc.title Hepatitis C virus infection inhibits P-body granule formation in human liversca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/acceptedVersionca