Hepatitis delta antigen and hepatitis delta virus ribonucleoprotein complex (HDAg-HDV RNP)

The Hepatitis Delta Antigen (HDAg) and the associated Hepatitis Delta Virus (HDV) ribonucleoprotein (RNP) complex are the core functional units of the HDV infectious agent, a satellite virus that requires Hepatitis B Virus (HBV) for its envelope and transmission (UniProt: P03334). The HDAg protein exists in two isoforms: the small HDAg (S-HDAg), which is essential for initiating and maintaining viral RNA replication, and the large HDAg (L-HDAg), which acts as a dominant-negative inhibitor of replication and is required for viral assembly (PubMed: 25130618). A critical step in the HDV life cycle is the post-translational farnesylation of L-HDAg at its C-terminal CXXX box, a modification that allows the RNP complex to interact with HBV surface antigens (HBsAg) to form mature, infectious virions (PubMed: 21614085). This farnesylation process is a major therapeutic target; farnesyltransferase inhibitors like Lonafarnib disrupt the morphogenesis of the virus by preventing the assembly of the RNP into the viral envelope (NIH: NCT03719313). Chronic HDV infection, driven by the persistence of this RNP complex, is the most severe form of human viral hepatitis, often leading to rapid progression to cirrhosis and an increased risk of hepatocellular carcinoma (WHO: Hepatitis D).

Other names

HDAgSmall hepatitis delta antigen (S-HDAg)Large hepatitis delta antigen (L-HDAg)HDV ribonucleoprotein complexHepatitis D virus antigenHDV RNP

Farnesyltransferase inhibition