A cultured cell receptor for the small S protein of hepatitis B virus

Human hepatitis B virus (HBV) has not been passaged in established cell culture systems. To determine whether this inability results from the lack of a receptor, 30 cell lines were examined for their abilities to bind 125I-labeled recombinant hepatitis B virus surface antigen (rHBsAg) particles. These particles contained only the small surface (S) protein, which is also found in the envelope of infectious HBV particles. Only two cells lines, both derived from African green monkey kidney, were able to bind a large portion of the 125I-rHBsAg particles. Binding to one of these cell lines, Vero, was found to be specific by three criteria: it was competitively inhibited by nonradioactive particles, it was saturable, and it could be blocked by chimpanzee antiserum raised against the rHBsAg particles. Analysis of the binding data indicated a single major population of high affinity receptor sites: 2.7 X 10(5) sites/cell, Kd = 2.8 nM. Binding was not due to the covalently linked 125I tracer isotope because unlabeled particles also bound, as detected with a monoclonal antibody. Binding was not unique to this recombinant particle preparation since serum-derived particles also bound to Vero cells. These results indicate that the Vero cell line expresses a receptor for the small S protein of HBV and that the small S protein, alone, may function as the HBV attachment protein.