The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus

We discovered that the hepatitis C virus (HCV) envelope glycoprotein E2 binds to human hepatoma cell lines independently of the previously proposed HCV receptor CD81. Comparative binding studies using recombinant E2 from the most prevalent 1a and 1b genotypes revealed that E2 recognition by hepatoma...

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Bibliographic Details
Published in:The EMBO journal 2002-10, Vol.21 (19), p.5017-5025
Main Authors: Scarselli, Elisa, Ansuini, Helenia, Cerino, Raffaele, Roccasecca, Rosa Maria, Acali, Stefano, Filocamo, Gessica, Traboni, Cinzia, Nicosia, Alfredo, Cortese, Riccardo, Vitelli, Alessandra
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - physiology
Carcinoma, Hepatocellular
CD36 Antigens - physiology
CHO Cells
Cloning, Molecular
Cricetinae
EMBO19
EMBO23
Flow Cytometry
Genotypes
Hepacivirus - physiology
Hepatitis
hepatitis C virus
Humans
hypervariable region 1
Leukemia, T-Cell
Liver Neoplasms
Membrane Proteins - physiology
Receptors, Immunologic
Receptors, Lipoprotein - physiology
Receptors, Scavenger
Receptors, Virus - physiology
Recombinant Proteins - metabolism
scavenger receptor class B type I
Scavenger Receptors, Class B
second envelope glycoprotein
Tetraspanin 28
Tumor Cells, Cultured
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Summary:We discovered that the hepatitis C virus (HCV) envelope glycoprotein E2 binds to human hepatoma cell lines independently of the previously proposed HCV receptor CD81. Comparative binding studies using recombinant E2 from the most prevalent 1a and 1b genotypes revealed that E2 recognition by hepatoma cells is independent from the viral isolate, while E2–CD81 interaction is isolate specific. Binding of soluble E2 to human hepatoma cells was impaired by deletion of the hypervariable region 1 (HVR1), but the wild‐type phenotype was recovered by introducing a compensatory mutation reported previously to rescue infectivity of an HVR1‐deleted HCV infectious clone. We have identified the receptor responsible for E2 binding to human hepatic cells as the human scavenger receptor class B type I (SR‐BI). E2–SR‐BI interaction is very selective since neither mouse SR‐BI nor the closely related human scavenger receptor CD36, were able to bind E2. Finally, E2 recognition by SR‐BI was competed out in an isolate‐specific manner both on the hepatoma cell line and on the human SR‐BI‐transfected cell line by an anti‐HVR1 monoclonal antibody.
ISSN:0261-4189
1460-2075
DOI:10.1093/emboj/cdf529