PROTEASE-ACTIVATED LYMPHOID-CELL AND HEPATOCYTE RECOGNITION SITE IN THE PRES1 DOMAIN OF THE LARGE WOODCHUCK HEPATITIS-VIRUS ENVELOPE PROTEIN

A site capable of strictly host- and cell type-specific recognition wa s identified in the preS1 domain of woodchuck hepatitis virus (WHV) th rough the use of antipeptide antisera generated against the extreme N- terminal fragment of the large virus envelope protein, The crucial det erminant of this binding site was mapped to amino acids 10-13. Althoug h a synthetic analogue of the site was highly immunogenic, natural WHV envelope did not display the site activity unless it was modified by proteolysis or acidic pH treatment, indicating an internal location of the determinant in viral envelope, Synthetic peptides encompassing th e sequence of this site bound woodchuck lymphoid cells and hepatocytes in a species-restricted manner which followed characteristics of a sp ecific ligand-receptor interaction, although their ability to interact with lymphoid cells was considerably greater than that for hepatocyte s. In WHV-infected animals, a natural antibody to the identified crypt ic cell-binding site arose independently of that directed against epit opes of unmodified virus envelope and its appearance constituted the e arliest immunovirological indicator of virus invasion, Our results dem onstrated that the preS1 domain of the large WHV envelope protein is e ndowed with the species- and cell type-specific recognition site which is protected against antibody surveillance by the natural tertiary st ructure of the protein and we suggest that proteolytic cleavage is req uired to induce the binding activity.