Squamous cell carcinoma antigen 1-mediated binding of hepatitis B virus to hepatocytes does not involve the hepatic serpin clearance system.
The cellular receptor for hepatitis B virus (HBV) has not yet been identified. A recent candidate is a homologue of squamous cell carcinoma antigen 1 (SCCA1), a serpin. This study confirms that transfection of SCCA1 into mammalian cells (both hepatocyte-derived and of non-hepatocyte origin) results in increased HBV binding. Furthermore, virus bound to transfected cells is protected significantly from degradation by trypsin (75% compared with 30% in untransfected cells). The possibility that HBV enters cells via the hepatic clearance system for serpin-enzyme complexes was investigated by analysis of the reactive site loop of SCCA1. Functional and deletion mutants of SCCA1 were constructed by site-directed mutagenesis and compared with the wild type construct. In no case was virus binding reduced by functional alterations or deletions within the reactive site loop. A possible role for the low density lipoprotein receptor-related protein (LRP) in binding virus was investigated. SCCA1 transfection of Huh7 cells was shown to result in up-regulation of LRP expression, reaching levels observed in total liver. However, the use of receptor-associated protein (RAP), a competitive ligand for LRP, suggests than LRP up-regulation is not responsible for enhanced virus binding to SCCA1-transfected cells.
Moore
Penelope L
PL
Centre for Hepatology, Department of Medicine, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, United Kingdom.
Ong
Sarah
S
Harrison
Tim J
TJ
D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D006515:Hepatitis B virus / Q000378:metabolism* / Q000502:physiology; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D008099:Liver / Q000502:physiology; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism / Q000502:physiology; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011991:Receptors, Virus; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D000951:Antigens, Neoplasm; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011991:Receptors, Virus; D015843:Serpins; C051072:squamous cell carcinoma-related antigen