Hepatitis delta virus (HDV) is a defective RNA virus which is dependent on hepatitis B virus for essential helper functions. Only a single highly basic
phosphoprotein, HDV
antigen (
HDAg), is expressed by the HDV genome during
infection in humans. Antibody directed to
HDAg is important in the diagnosis of HDV
infection, and it is likely but not yet proven that the immune response to
HDAg provides significant protection against subsequent exposures to HDV. In an effort to map the antigenic domains of
HDAg, 209 overlapping hexapeptides, spanning the entire 214
amino acid residues of the
protein, were synthesized on
polyethylene pins and probed by
enzyme-linked
immunosorbent assay with sera containing high titers of anti-HD
antibodies. Domains recognized by
antibodies present in serum from human chronic carriers of this virus included residues 2 to 7, 63 to 74, 86 to 91, 94 to 100, 159 to 172, 174 to 195, and 197 to 207. Antibody from an acutely superinfected woodchuck recognized similar
epitopes, as well as a domain spanning residues 121 to 128. Together, residues in these antigenic domains constitute 41% of the
HDAg molecule.
Oligopeptides 15 to 29 residues in length and representing
epitopes of
HDAg found to be dominant in humans (residues 2 to 17, 156 to 184, and 197 to 211) were synthesized in bulk and found to possess significant antigenic activity by microdilution
enzyme-linked
immunosorbent assay. The reactivity of
peptide 197-211 with human sera confirms that the entire 214
amino acids of
HDAg are expressed during
infection in vivo. In addition, these results suggest that synthetic
peptides may be useful
reagents for development of new and improved diagnostic tests for HDV
infection.