Ym. Jin et al., PROTEASE-ACTIVATED LYMPHOID-CELL AND HEPATOCYTE RECOGNITION SITE IN THE PRES1 DOMAIN OF THE LARGE WOODCHUCK HEPATITIS-VIRUS ENVELOPE PROTEIN, Journal of General Virology, 77, 1996, pp. 1837-1846
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.