title: Hepatitis C virus infection inhibits P-body granule formation in human livers.
abstract: OBJECTIVE
  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.
authors.affiliation: Molecular Virology, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Pérez-Vilaró
authors.affiliation: Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-Carrillo
authors.affiliation: Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Mensa
authors.affiliation: Pathology Department, Hospital Clínic, Barcelona, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Miquel
authors.affiliation: Scientific and Technical Services, Universitat Pompeu Fabra, Barcelona, Spain; Advanced Light Microscopy Unit, Center for Genomic Regulation, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Sanjuan
authors.affiliation: Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Forns
authors.affiliation: Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, Barcelona, Spain. Electronic address: sofiapp@clinic.ub.es.
authors.forename: Sofía
authors.initials: S
authors.lastname: Pérez-del-Pulgar
authors.affiliation: Molecular Virology, Universitat Pompeu Fabra, Barcelona, Spain. Electronic address: juana.diez@upf.edu.
authors.forename: Juana
authors.initials: J
authors.lastname: Díez
mesh_terms: D000328:Adult; D003594:Cytoplasmic Granules / Q000502:physiology*; D053487:DEAD-box RNA Helicases / Q000096:biosynthesis / Q000276:immunology; D010450:Endopeptidases / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D016174:Hepacivirus / Q000472:pathogenicity / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000276:immunology; D019562:Viral Load
chemical_list: D011518:Proto-Oncogene Proteins; D010450:Endopeptidases; C020071:dipeptidyl carboxypeptidase; C094683:DDX6 protein, human; D053487:DEAD-box RNA Helicases
keywords: HCV; Liver; P-bodies; in vivo