Immunohistochemical Detection of Hepatitis Delta Antigen

There is only one antigen specifically associated with the hepatitis delta virus (HDV) infection, i.e., the hepatitis delta antigen (HDAg) (1 ,2 ). HDAg is a phosphoprotein encoded by an open reading frame conserved among all HDV isolates. HDAg is a structural protein, because approx 200 subunits of HDAg bind via specific domains to genomic RNA, forming a core-like structure within an envelope provided by the co-infecting helper hepadnavirus (3 ). HDAg consists of two protein species of 24 kDa (195 amino acids) and 27 kDa (214 amino acids), referred to as small HDAg (S-HDAg) and large HDAg (L-HDAg), respectively. Those two proteins share the same primary structure, except for a unique 19-amino-acid sequence found at the C-terminus of L-HDAg, which possesses packaging activity. This additional sequence found in L-HDAg is synthesized via an RNA-editing process during HDV replication.