Hepatitis delta virus RNA–hepatitis delta antigen interaction (HDV RNA–HDAg interaction)

The Hepatitis Delta Virus (HDV) RNA–hepatitis delta antigen (HDAg) interaction is the foundational step in forming the viral ribonucleoprotein (RNP) complex required for viral assembly and morphogenesis (Taylor, 2006, Journal of Virology). HDV is a unique human pathogen that lacks its own envelope proteins, instead hijacking the Hepatitis B virus (HBV) surface antigens (HBsAg) to package its genome (Alves et al., 2013, Journal of Virology). The interaction involves the circular, single-stranded HDV RNA genome and two isoforms of HDAg: the small antigen (S-HDAg), which facilitates RNA replication, and the large antigen (L-HDAg), which contains a prenylation signal necessary for virion assembly (Wang et al., 1994, Journal of Virology). During morphogenesis, L-HDAg binds to the HDV RNA and subsequently interacts with HBsAg, facilitating the budding of new virions from the host cell (Koh et al., 2011, Journal of Infectious Diseases). This interaction is a high-value therapeutic target because disrupting the RNP formation or its association with the HBV envelope effectively halts the production of infectious HDV particles. Pharmacological agents such as Lonafarnib target this pathway by inhibiting farnesyltransferase, the enzyme responsible for the prenylation of L-HDAg, thereby preventing the RNP-envelope interaction (Wedemeyer et al., 2019, The Lancet Infectious Diseases). Clinical management of HDV infection focuses on these assembly inhibitors to reduce viral load and mitigate the risk of cirrhosis and hepatocellular carcinoma (Hughes et al., 2011, Lancet).

Other names

HDV ribonucleoprotein assemblyHDV RNP formationHDAg-RNA bindingHepatitis delta virus morphogenesis complex

Inhibition of viral assembly and morphogenesis by disrupting the formation of the HDV ribonucleoprotein complex or its association with the Hepatitis B surface antigen envelope.