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

The Hepatitis D virus (HDV) RNA–hepatitis D antigen (HDAg) interaction is the fundamental process by which the viral genome associates with its only encoded protein to form a ribonucleoprotein (RNP) complex (NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109463/). This interaction is essential for every stage of the HDV life cycle, including the nuclear import of the viral genome, the initiation and elongation of RNA replication by host RNA polymerase II, and the eventual assembly of new virions (MDPI, https://www.mdpi.com/1999-4915/15/7/1544). HDAg exists in two isoforms: the small form (S-HDAg), which promotes replication, and the large form (L-HDAg), which inhibits replication and facilitates packaging by interacting with the hepatitis B surface antigen (HBsAg) (Wikipedia, https://en.wikipedia.org/wiki/Hepatitis_delta_virus). Disrupting this interaction or the subsequent functions of the RNP complex is a major therapeutic strategy for treating chronic hepatitis D, the most severe form of human viral hepatitis (PNAS, https://www.pnas.org/doi/10.1073/pnas.2315444121). While current therapies like lonafarnib target the post-translational modification of HDAg to prevent assembly, and bulevirtide blocks viral entry, the RNA-HDAg interaction itself remains a critical focal point for developing direct-acting antivirals (Gastroenterology & Hepatology, https://www.gastroenterologyandhepatology.net/archives/july-2019/new-and-emerging-therapies-for-hepatitis-d/).

Other names

HDV ribonucleoprotein assemblyHDAg–RNA bindingHepatitis D ribonucleoprotein complexHDAg–HDV RNA interactionHDV RNP formation

Inhibition of the formation or function of the HDV ribonucleoprotein complex, thereby blocking viral replication, nuclear transport, and assembly with the helper virus envelope.