A small open reading frame of the hepatitis delta virus antigenomic RNA encodes a protein that elicits antibodies in some infected patients.

A small open reading frame (ORF) was found in the hepatitis delta virus (HDV) antigenomic RNA encoding a short peptide that shares structural similarity with a region of the hepatitis B virus terminal protein. Analysis of all published HDV genome sequences indicates a high degree of conservation for the small ORF. This ORF is located at the 3'-terminal region of the gene encoding the hepatitis delta antigen (HDAg). We speculated that a peptide encoded by this ORF can be represented as the C-terminal domain of a new protein called HDAg'. This protein contains almost the entire sequence represented in the small form of HDAg and a peptide as an additional 'extension' sequence at the C-terminus. Two long synthetic peptides representing the two different types of peptides encoded by the small ORF were synthesized. These peptides were used for the development of an immunoassay for the detection of antibody to the HDAg' specific domain in sera of patients with HDV infection. Among 162 serum samples analyzed, 13 were found to be positive for an antibody reactive with these synthetic peptides. These antibodies were identified in patients with HDV infections and were not found in patients infected with hepatitis B virus, hepatitis C virus, or non-A,non-B,non-C virus. Thus, these data support the identification and existence of a new antigen encoded by the antigenomic RNA of the HDV.