Hepatitis delta antigen (HDAg)

Hepatitis delta antigen (HDAg) is the sole protein encoded by the Hepatitis D virus (HDV) genome, a satellite virus that requires the presence of Hepatitis B virus (HBV) for its life cycle (UniProt P03334). HDAg exists in two distinct isoforms: the small form (S-HDAg), which is essential for initiating and sustaining viral RNA replication, and the large form (L-HDAg), which is produced via RNA editing by host ADAR1 (PubMed: 32690478). L-HDAg acts as a transdominant inhibitor of replication and is critical for viral assembly, as its C-terminal prenylation (farnesylation) allows it to interact with HBV surface antigens (HBsAg) to form mature virions (NIH/NCBI). Chronic HDV infection is the most severe form of viral hepatitis, often leading to rapid progression to cirrhosis and hepatocellular carcinoma (Wikipedia). Therapeutic strategies targeting HDAg primarily focus on inhibiting the post-translational farnesylation of L-HDAg using farnesyltransferase inhibitors like lonafarnib (PubMed: 32690478). By preventing this modification, the virus is unable to assemble and exit the hepatocyte, thereby reducing the viral load and slowing disease progression.

Other names

Small hepatitis delta antigenLarge hepatitis delta antigenDelta antigenHDV-AgS-HDAgL-HDAg

Inhibition of host farnesyltransferase to prevent the post-translational farnesylation of the Large Hepatitis Delta Antigen (L-HDAg), which is essential for its interaction with HBsAg and subsequent viral assembly and secretion.