An 80-kilodalton protein that binds to the pre-S1 domain of hepatitis B virus

It has been suggested that hepatitis B virus (HBV) binds to a receptor on t he plasma membrane of human hepatocytes via the pre-Si domain of the large envelope protein as an initial step in HBV infection, However, the nature o f the receptor remains controversial, In an attempt to identify a cell surf ace receptor for HBV, purified recombinant fusion protein of the pre-SI dom ain of HBV with glutathione S-transferase (GST), expressed in Escherichia r oll, was used as a ligand, The surface of human hepatocytes or HepG2 cells was biotinylated, and the cell lysate (precleared lysate) which did not bin d to GST and glutathione-Sepharose beads was used as a source of receptor m olecules. The precleared lysate of the biotinylated cells was incubated wit h the GST-pre-S1 fusion protein, and the bound proteins were visualized by Western blotting and enhanced chemiluminescence, An approximately 80-kDa pr otein (p80) was shown to bind specifically to the pre-SI domain of the fusi on protein, The receptor binding assay using serially or internally deleted segments of pre-S1 showed that amino acid residues 12 to 20 and 82 to 90 a re essential for the binding of pre-SI to p80, p80 also bound specifically to the pre-SI of native HBV particles, Analysis of the tissue and species s pecificity of p80 expression in several available human primary cultures an d cell lines of different tissue origin showed that p80 expression is not r estricted to human hepatocytes, Taken together the results suggest that p80 may be a component of the viral entry machinery.