Hepatitis C virus receptors claudin-1 and occludin after liver transplantation and influence on early viral kinetics§

Authors

  • Laura Mensa,

    1. Liver Unit, Hospital Clinic, IDIBAPS, Ciberehd, Barcelona, Spain
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    • LM and GC contributed equally to this study and both should be considered first authors.

  • Gonzalo Crespo,

    1. Liver Unit, Hospital Clinic, IDIBAPS, Ciberehd, Barcelona, Spain
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    • LM and GC contributed equally to this study and both should be considered first authors.

  • Matthew J. Gastinger,

    1. Biological Imaging Facility/Research Technologies Branch, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD
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  • Juraj Kabat,

    1. Biological Imaging Facility/Research Technologies Branch, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD
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  • Sofía Pérez-del-Pulgar,

    1. Liver Unit, Hospital Clinic, IDIBAPS, Ciberehd, Barcelona, Spain
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  • Rosa Miquel,

    1. Pathology Department, Hospital Clinic, IDIBAPS, Ciberehd, Barcelona, Spain
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  • Suzanne U. Emerson,

    1. Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD
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  • Robert H. Purcell,

    1. Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD
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  • Xavier Forns

    Corresponding author
    1. Liver Unit, Hospital Clinic, IDIBAPS, Ciberehd, Barcelona, Spain
    • Liver Unit, Institut de Malalties Digestives, Hospital Clinic, IDIBAPS, Ciberehd, Villarroel 170, 08036 Barcelona, Spain
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    • Potential conflicts of interest: X.F. received an unrestricted grant support from Schering and Roche. M.G. is currently employed by Bitplane but his affiliation was the one stated above during the period of study design, laboratory work, and article preparation.


  • X. Forns received support in part by a grant from Instituto de Salud Carlos III (PI080239), cofunded by the European Regional Development Fund (ERDF), and by the Spanish Association for the Study of Liver Diseases (AEEH, Beca Hernández-Guío). G. Crespo was supported by Hospital Clinic (Ajut a la Recerca Josep Font) and Fundación BBVA. L. Mensa was supported by Instituto de Salud Carlos III (PFIS). This study was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

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. (HEPATOLOGY 2011;.)

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