Hepatitis C virus receptor expression in normal and diseased liver tissue.
The principal site of hepatitis C virus (HCV) replication is the liver. HCV pseudoparticles infect human liver derived cell lines and this suggests that liver-specific receptors contribute to defining HCV hepatotropism. At least three host cell molecules have been reported to be important for HCV entry: the tetraspanin CD81, scavenger receptor class B member I (SR-BI), and the tight junction (TJ) protein Claudin 1 (CLDN1). Hepatocytes in liver tissue coexpress CD81, SR-BI, and CLDN1, consistent with their ability to support HCV entry. CLDN1 localized at the apical-canalicular TJ region and at basolateral-sinusoidal hepatocyte surfaces in normal tissue and colocalized with CD81 at both sites. In contrast, CLDN1 appeared to colocalize with SR-BI at the basolateral-sinusoidal surface. CLDN1 expression was increased on basolateral hepatocyte membranes in HCV-infected and other chronically inflamed liver tissue compared with normal liver. In contrast, CLDN4 hepatocellular staining was comparable in normal and diseased liver tissue.


CONCLUSIONS
HCV infection of Huh-7.5 hepatoma cells in vitro significantly increased CLDN1 expression levels, consistent with a direct modulation of CLDN1 by virus infection. In HCV infected livers, immunohistochemical studies revealed focal patterns of CLDN1 staining, suggesting localized areas of increased CLDN1 expression in vivo which may potentiate local viral spread within the liver.
Reynolds
Gary M
GM
Liver Laboratories, Institute for Biomedical Research, University of Birmingham and University Hospital Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
Harris
Helen J
HJ
Jennings
Adam
A
Hu
Ke
K
Grove
Joe
J
Lalor
Patricia F
PF
Adams
David H
DH
Balfe
Peter
P
Hübscher
Stefan G
SG
McKeating
Jane A
JA
D000918:Antibody Specificity; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D018955:CD36 Antigens / Q000235:genetics*; D002460:Cell Line; D062445:Claudin-1; D016174:Hepacivirus / Q000502:physiology*; D006498:Hepatectomy; D006526:Hepatitis C / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000473:pathology / Q000821:virology*; D008103:Liver Cirrhosis / Q000601:surgery; D008107:Liver Diseases / Q000473:pathology / Q000601:surgery / Q000821:virology*; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D011991:Receptors, Virus / Q000235:genetics*; D013601:T-Lymphocytes / Q000821:virology; D060225:Tetraspanin 28; D014779:Virus Replication
D015703:Antigens, CD; D018955:CD36 Antigens; C554798:CD81 protein, human; C568108:CLDN1 protein, human; D062445:Claudin-1; D008565:Membrane Proteins; D011991:Receptors, Virus; D060225:Tetraspanin 28