title: Hepatitis C virus receptors claudin-1 and occludin after liver transplantation and influence on early viral kinetics.
abstract: Liver transplantation (LT) is a unique model to study hepatitis C virus (HCV) entry into hepatocytes. Recent in vitro studies suggest significant changes in the expression of the HCV receptors claudin-1 and occludin after HCV infection. Our aims were: (1) to characterize claudin-1 and occludin expression in grafts from LT recipients and (2) to explore their potential influence on early HCV kinetics and their changes after HCV infection. We included 42 HCV-infected LT recipients and 19 uninfected controls. Claudin-1 and occludin were detected in paraffin-embedded liver biopsies obtained during reperfusion and 3 and 12 months after LT. HCV receptors were characterized by confocal immunofluorescence microscopy; quantification and colocalization studies were performed with dedicated software. Claudin-1 and occludin expression were restricted to the apical pole of hepatocytes. There was a significant correlation between the amount of scavenger receptor B1 at the time of reperfusion and the HCV-RNA decay during the first 24 hours following LT (r = 0.55, P = 0.007). Similarly, there was a significant correlation between the levels of claudin and occludin and the slope of HCV-RNA increase during the first week after LT (r = 0.63, P = 0.005). Occludin and claudin-1 levels increased significantly 12 months after LT (P = 0.03 and P = 0.007, respectively). The expression pattern of both proteins, however, remained unchanged, colocalizing strongly (60%-94%) at the apical membrane of hepatocytes.
  
  
  CONCLUSIONS
  HCV receptor levels at the time of LT seem to modulate early HCV kinetics. Hepatitis C recurrence after LT was associated with increased levels of claudin-1 and occludin in the hepatocyte cell membrane, although it did not alter their localization within the tight junctions.
authors.affiliation: Liver Unit, Hospital Clinic, IDIBAPS, Ciberehd, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Mensa
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Crespo
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gastinger
authors.forename: Juraj
authors.initials: J
authors.lastname: Kabat
authors.forename: Sofía
authors.initials: S
authors.lastname: Pérez-del-Pulgar
authors.forename: Rosa
authors.initials: R
authors.lastname: Miquel
authors.forename: Suzanne U
authors.initials: SU
authors.lastname: Emerson
authors.forename: Robert H
authors.initials: RH
authors.lastname: Purcell
authors.forename: Xavier
authors.initials: X
authors.lastname: Forns
mesh_terms: D000328:Adult; D000368:Aged; D062445:Claudin-1; D005260:Female; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000821:virology*; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D062793:Occludin; D011991:Receptors, Virus / Q000096:biosynthesis*; D012189:Retrospective Studies
chemical_list: C568108:CLDN1 protein, human; D062445:Claudin-1; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D011991:Receptors, Virus