The HDV genome is a unique chimaeric molecule with some of the properties of a satellite virus and some of a viroid - a covalently closed circular RNA molecule 1679-1683 bases long with a branched or rod-like configuration:
This molecule is thought to be replicated by host cell RNA polymerase II using a rolling circle mechanism. This produces linear concatemers which must be cleaved for infetcivity. The cleavage is carried out by a ribozyme domain present in the HDV RNA, the only known example of a ribozyme in an animal virus genome ("Crystal structure of a hepatitis delta virus ribozyme" Nature 395: 567-574, 1998).
However, unlike all other viroids, HDV encodes a protein, the delta antigen, which is a nuclear phosphoprotein. Post-transcriptional RNA editing results in the production of two slightly different forms of the protein, S-HDAg (195 amino acids) which is necessary for HDV replication and L-HDAg (214 amino acids) which is necessary for the assembly and release of HDV-containing particles. Preparations from HDV-infected animals contain heterologous particles distinct from HBV but with ill-defined structure. L-HDAg and small-form hepatitis B surface antigen (HBsAg) of the helper hepatitis B virus have previously been shown to be the minimum components for the assembly of these particles.
Replication of HDV is hard to study since it requires the presence of a helper virus (HBV) which itself cannot be cultured! HDV can be controlled by controlling HBV infection. The worldwide distributions of HDV infection is currently changing as HBV vaccination programmes begin to take effect, for example in Italy: in a study of HBsAg chronic carriers, HDV prevalence reduced from 23% in 1987 to 14% in 1992.