Scavenger receptor class B type I and hepatitis C virus infection of primary tupaia hepatocytes.
Hepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide. The study of early steps during HCV infection has been hampered by the lack of suitable in vitro or in vivo models. Primary Tupaia hepatocytes (PTH) have been shown to be susceptible to HCV infection in vitro and in vivo. Human scavenger receptor class B type I (SR-BI) represents an HCV receptor candidate mediating the cellular binding of E2 glycoprotein to HepG2 hepatoma cells. However, the function of SR-BI for viral infection of hepatocytes is unknown. In this study, we used PTH to assess the functional role of SR-BI as a putative HCV receptor. Sequence analysis of cloned tupaia SR-BI revealed a high homology between tupaia and human SR-BI. Transfection of CHO cells with human or tupaia SR-BI but not mouse SR-BI cDNA resulted in cellular E2 binding, suggesting that E2-binding domains between human and tupaia SR-BI are highly conserved. Preincubation of PTH with anti-SR-BI antibodies resulted in marked inhibition of E2 or HCV-like particle binding. However, anti-SR-BI antibodies were not able to block HCV infection of PTH. In conclusion, our results demonstrate that SR-BI represents an important cell surface molecule for the binding of the HCV envelope to hepatocytes and suggest that other or additional cell surface molecules are required for the initiation of HCV infection. Furthermore, the structural and functional similarities between human and tupaia SR-BI indicate that PTH represent a useful model system to characterize the molecular interaction of the HCV envelope and SR-BI on primary hepatocytes.
Barth
Heidi
H
Dept. of Medicine II, University of Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany.
Cerino
Raffaele
R
Arcuri
Mirko
M
Hoffmann
Marco
M
Schürmann
Peter
P
Adah
Mohammed I
MI
Gissler
Bettina
B
Zhao
Xiping
X
Ghisetti
Valeria
V
Lavezzo
Bruna
B
Blum
Hubert E
HE
von Weizsäcker
Fritz
F
Vitelli
Alessandra
A
Scarselli
Elisa
E
Baumert
Thomas F
TF
D000071443:12E7 Antigen; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D018955:CD36 Antigens; D015815:Cell Adhesion Molecules; D002478:Cells, Cultured; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000821:virology*; D022781:Hepatocytes / Q000821:virology; D008969:Molecular Sequence Data; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D051116:Receptors, Scavenger; D011991:Receptors, Virus / Q000235:genetics / Q000502:physiology*; D051122:Scavenger Receptors, Class B; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014417:Tupaia / Q000235:genetics; D014779:Virus Replication
D000071443:12E7 Antigen; D015703:Antigens, CD; D018955:CD36 Antigens; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D011991:Receptors, Virus; D051122:Scavenger Receptors, Class B