Life cycle and pathogenesis of hepatitis D virus: A review

Zaigham Abbas, Rafia Afzal

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)

Abstract

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-a 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 hostpathogen 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.

Original languageEnglish
Pages (from-to)666-675
Number of pages10
JournalWorld Journal of Hepatology
Volume5
Issue number12
DOIs
Publication statusPublished - Dec 2013
Externally publishedYes

Keywords

  • Hepatitis B virus
  • Hepatitis D virus
  • Hepatitis D virus pathogenicity
  • Hepatitis delta antigens
  • Hepatocellular carcinoma
  • Host-pathogen interactions
  • Interferonalpha
  • Virus replication

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