Molecular Biology



HDV RNA genome is single-stranded, negative sense, and small (approximately 1700 nucleotides) and consists of covalently closed circular RNA that is rod-shaped due to extensive base pairing. The genome is surrounded by a d antigen core encoded by HDV that is subsequently encased in an envelope embedded with Hepatitis B antigens (HBsAg).


FIGURE from Schiff's Diseases of the Liver, p. 787.

The virion measures 35-37 nm in diameter, approximately the same size as the HBV virion.


d Antigen

The d antigen exists as a small (24kDa) or large (24kDa) form. S-HDAg is required for RNA replication and is present in the infecting cell before replication begins.  L-HDAg is formed from an RNA editing event in one-third of antigenomic templates that translated beyond the normal stop codon used for the synthesis of S-HDAg. Produced later in infection, the large d antigen suppresses RNA genomic synthesis, limits cell destruction, and leads to encapsidation of RNA in progeny virions.

FIGURE Schematic diagram of HDV particles found in infectious serum. HDV virion consists of HBV envelope proteins HBsAg and ribonucleoprotein (RNP) that contains the circular genome RNA. |Citation: Sureau, Camille. Hepatitis Delta Virus: HDV-HBV Interactions. Hepatitis Delta Virus (2006).


Hepatitis Delta virus replication strategy is unique among all other animal viruses. After infection, HDV RNA is transferred to the nucleus, where replication and mRNA synthesis occur with the help of host cell DNA-dependent RNA polymerase II. Genomic RNA serves as a template to produce two RNAs: (1) a linear, polyadenylated mRNA that is translated into HDAg and (2) a covalently closed circular, positive-sense RNA that is complementary to the genomic RNA (antigenomic).

Replication occurs via a rolling circular method, seen only in plant viroids. HDV RNA synthesis begins at the origin and proceeds counterclockwise. The process generates the two types of RNAs (mentioned above) by cleavage of the synthesized RNA fragment by an HDV ribozyme, which is an RNA enzyme that catalyzes auto-cleavage. The ribozyme, which may also catalyze self-ligation, then converts the ssRNA molecules into circles. Antigenomic RNA that is produced can then be used as a circular template to produce full-length genomic RNA.