Published online Dec 27, 2013. doi: 10.4254/wjh.v5.i12.666
Revised: November 6, 2013
Accepted: November 15, 2013
Published online: December 27, 2013
Hepatitis D virus (HDV) is a defective RNA virus which requires the help of hepatitis B virus (HBV) virus for its replication and assembly of new virions. HDV genome contains only one actively transcribed open reading frame which encodes for two isoforms of hepatitis delta antigen. Post-translational modifications of small and large delta antigens (S-HDAg and L-HDAg) involving phosphorylation and isoprenylation respectively confer these antigens their specific properties. S-HDAg is required for the initiation of the viral genome replication, whereas L-HDAg serves as a principal inhibitor of replication and is essential for the assembly of new virion particles. Immune mediation has usually been implicated in HDV-associated liver damage. The pathogenesis of HDV mainly involves interferon-α signaling inhibition, HDV-specific T-lymphocyte activation and cytokine responses, and tumor necrosis factor-alpha and nuclear factor kappa B signaling. Due to limited protein coding capacity, HDV makes use of host cellular proteins to accomplish their life cycle processes, including transcription, replication, post-transcriptional and translational modifications. This intimate host-pathogen interaction significantly alters cell proteome and is associated with an augmented expression of pro-inflammatory, growth and anti-apoptotic factors which explains severe necroinflammation and increased cell survival and an early progression to hepatocellular carcinoma in HDV patients. The understanding of the process of viral replication, HBV-HDV interactions, and etio-pathogenesis of the severe course of HDV infection is helpful in identifying the potential therapeutic targets in the virus life cycle for the prophylaxis and treatment of HDV infection and complications.
Core tip: A scarcity of literature about the hepatitis D virus (HDV) life cycle and pathogenesis is clearly evident. Severity of HDV associated liver disease and lack of an efficient treatment regime therefore warrant urgent research into HDV biology. Virus entry inhibitors and isoprenylation inhibitors may play a role in preventing HDV superinfection and liver cirrhosis. As inhibition of interferon-α signaling by HDV plays a pivotal role in failure to clear the virus, testing interferon-free treatment regimens should undergo clinical trials. A low degree of heterogeneity in hepatitis delta antigen encourages the development of a vaccine using its immunogenic sequences.