title: Hepatitis delta virus: insights into a peculiar pathogen and novel treatment options.
abstract: Chronic hepatitis D is the most severe form of viral hepatitis, affecting ∼20 million HBV-infected people worldwide. The causative agent, hepatitis delta virus (HDV), is a unique human pathogen: it is the smallest known virus; it depends on HBV to disseminate its viroid-like RNA; it encodes only one protein (HDAg), which has both structural and regulatory functions; and it replicates using predominantly host proteins. The failure of HBV-specific nucleoside analogues to suppress the HBV helper function, and the limitations of experimental systems to study the HDV life cycle, have impeded the development of HDV-specific drugs. Thus, the only clinical regimen for HDV is IFNα, which shows some efficacy but long-term virological responses are rare. Insights into the receptor-mediated entry of HDV, and the observation that HDV assembly requires farnesyltransferase, have enabled novel therapeutic strategies to be developed. Interference with entry, for example through blockade of the HBV-HDV-specific receptor sodium/taurocholate cotransporting polypeptide NTCP by Myrcludex B, and inhibition of assembly by blockade of farnesyltransferase using lonafarnib or nucleic acid polymers such as REP 2139-Ca, have shown promising results in phase II studies. In this Review, we summarize our knowledge of HDV epidemiology, pathogenesis and molecular biology, with a particular emphasis on possible future developments.
authors.affiliation: Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.
authors.forename: Florian A
authors.initials: FA
authors.lastname: Lempp
authors.affiliation: Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.|German Center for Infection Research (DZIF), Heidelberg Partner Site, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.|German Center for Infection Research (DZIF), Heidelberg Partner Site, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Urban
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D019701:Hepatitis D, Chronic / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology; D003698:Hepatitis Delta Virus / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D054884:Host-Pathogen Interactions; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D055666:Lipopeptides / Q000627:therapeutic use; D009696:Nucleic Acids / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology; D003986:Dibenzocycloheptenes
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D055666:Lipopeptides; D009696:Nucleic Acids; D010880:Piperidines; D011725:Pyridines; C571888:myrcludex-B; C115354:lonafarnib; D003986:Dibenzocycloheptenes