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 was identified in the preS1 domain of woodchuck hepatitis virus (WHV) through the use of antipeptide antisera generated against the extreme N-terminal fragment of the large virus envelope protein. The crucial determinant of this binding site was mapped to amino acids 10-13. Although 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 the sequence of this site bound woodchuck lymphoid cells and hepatocytes in a species-restricted manner which followed characteristics of a specific ligand-receptor interaction, although their ability to interact with lymphoid cells was considerably greater than that for hepatocytes. In WHV-infected animals, a natural antibody to the identified cryptic cell-binding site arose independently of that directed against epitopes of unmodified virus envelope and its appearance constituted the earliest immunovirological indicator of virus invasion. Our results demonstrated that the preS1 domain of the large WHV envelope protein is endowed with the species- and cell type-specific recognition site which is protected against antibody surveillance by the natural tertiary structure of the protein and we suggest that proteolytic cleavage is required to induce the binding activity.
Jin
Y M
YM
Division of Basic Medical Sciences, Faculty of Medicine, Health Sciences Centre, Memorial University of Newfoundland, St John's, Canada.
Churchill
N D
ND
Michalak
T I
TI
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D010450:Endopeptidases / Q000378:metabolism*; D018985:Epitopes, B-Lymphocyte; D006509:Hepatitis B / Q000276:immunology / Q000662:veterinary / Q000821:virology; D006510:Hepatitis B Antibodies / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000276:immunology / Q000502:physiology; D017919:Hepatitis B Virus, Woodchuck / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000821:virology*; D008214:Lymphocytes / Q000821:virology*; D008392:Marmota; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000737:chemistry / Q000276:immunology / Q000502:physiology; D051381:Rats; D013045:Species Specificity; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology / Q000502:physiology*
D018985:Epitopes, B-Lymphocyte; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; C096362:L protein, hepatitis B virus; D011498:Protein Precursors; D014759:Viral Envelope Proteins; C050806:presurface protein 1, hepatitis B surface antigen; D010450:Endopeptidases