Hepatitis D

Hepatitis D
Hepatitis D
Virus classification
Group: Group V ((-)ssRNA)
Order: Unassigned
Family: Unassigned
Genus: Deltavirus
Species: Hepatitis delta virus
Hepatitis D
Classification and external resources
ICD-10 B17.0, B18.0
ICD-9 070.31
MeSH D003699

Hepatitis D, also referred to as hepatitis D virus (HDV) and classified as Hepatitis delta virus, is a disease caused by a small circular enveloped RNA virus. It is one of five known hepatitis viruses: A, B, C, D, and E. HDV is considered to be a subviral satellite because it can propagate only in the presence of the hepatitis B virus (HBV).[1] Transmission of HDV can occur either via simultaneous infection with HBV (coinfection) or superimposed on chronic hepatitis B or hepatitis B carrier state (superinfection).

Both superinfection and coinfection with HDV results in more severe complications compared to infection with HBV alone. These complications include a greater likelihood of experiencing liver failure in acute infections and a rapid progression to liver cirrhosis, with an increased chance of developing liver cancer in chronic infections.[2] In combination with hepatitis B virus, hepatitis D has the highest mortality rate of all the hepatitis infections of 20%.




Hepatitis D virus was first reported in the mid-1970s, as a nuclear antigen in patients infected with HBV who had severe liver disease [3] This nuclear antigen was then thought to be a hepatitis B antigen and was called the delta antigen. Subsequent experiments in chimpanzees showed that the hepatitis delta antigen (HDAg) was a structural part of a pathogen that required HBV infection to replicate[4] The entire virus was cloned and sequenced in 1986, and obtained its own genus deltavirus [5][6]

Structure and Genome

Hepatitis delta virus delta antigen
PDB 1a92 EBI.jpg
oligomerization domain of hepatitis delta antigen
Symbol HDV_ag
Pfam PF01517
InterPro IPR002506
SCOP 1a92

The HDV is a small, spherical virus with a 36 nm diameter. It has an outer coat containing three HBV envelope proteins (called large, medium, and small hepatitis B surface antigens, and host lipids surrounding an inner nucleocapsid. The nucleocapsid contains single-stranded, circular RNA of 1679 nucleotides and about 200 molecules of hepatitis D antigen (HDAg) for each genome. The central region of HDAg has been shown to bind RNA.[7] Several interactions are also mediated by a coiled-coil region at the N terminus of HDAg.[8] The hepatitis D circular genome is unique to animal viruses because of its high GC nucleotide content. The HDV genome exists as an enveloped negative sense, single-stranded, closed circular RNA nucleotide sequence is 70% self-complementary, allowing the genome to form a partially double stranded RNA structure that is described as rod-like.[9] With a genome of approximately 1700 nucleotides, HDV is the smallest "virus" known to infect animals. It has been proposed that HDV may have originated from a class of plant viruses called viroids.[10][11]

There are at least 8 genotypes of this virus (HDV-1 to HDV-8).[12]

Life Cycle

The receptor that HDV recognizes on human hepatocytes has not been identified; however it is thought to be the same as the HBV receptor because both viruses have the same outer coat.[13] HDV recognizes its receptor via the N-terminal domain of the large hepatitis B surface antigen, HBsAg.[14] Mapping by mutagenesis of this domain has shown that aminoacid residues 9-15 make up the receptor binding site.[15] After entering the hepatocyte, the virus is uncoated and the nucleocapsid translocated to the nucleus due to a signal in HDAg[16] Since the nucleocapsid does not contain an RNA polymerase to replicate the virus’ genome, the virus makes use of the cellular RNA polymerases Initially just RNA pol II,[17][18] now RNA polymerases I and III have also been shown to be involved in HDV replication[19] Normally RNA polymerase II utilizes DNA as a template and produces mRNA. Consequently, if HDV indeed utilizes RNA polymerase II during replication, it would be the only known pathogen capable of using a DNA-dependent polymerase as an RNA-dependent polymerase.

The RNA polymerases treat the RNA genome as double stranded DNA due to the folded rod-like structure it is in. Three forms of RNA are made; circular genomic RNA, circular complementary antigenomic RNA, and a linear polyadenylated antigenomic RNA, which is the mRNA containing the open reading frame for the HDAg. Synthesis of antigenomic RNA occurs in the nucleous, mediated by RNA Pol I, whereas synthesis of genomic RNA takes place in the nucleoplasm, mediated by RNA Pol II.[20] HDV RNA is synthesized first as linear RNA that contains many copies of the genome. The genomic and antigenomic RNA contain a sequence of 85 nucleotides that acts as a ribozyme, which self-cleaves the linear RNA into monomers. This monomers are then ligated to form circular RNA [21][22]

There are eight reported genotypes of HDV with unexplained variations in their geographical distribution and pathogenicity.

Delta antigens

A significant difference between viroids and HDV is that, while viroids produce no proteins, HDAg is the only protein known to be coded for by the HDV genome. It consist of two forms; a 27kDa large-HDAg, and a small-HDAg of 24kDa. The N-terminals of the two forms are identical, they differ by 19 more amino acids in the C-terminal of the large HDAg.[23] Both isoforms are produced from the same reading frame which contains an UAG stop codon at codon 196, which normally produces only the small-HDAg. However, editing by cellular enzyme adenosine deaminase-1 changes the stop codon to UCG, allowing the large-HDAg to be produced [23][24] Despite having 90% identical sequences, these two proteins play diverging roles during the course of an infection. HDAg-S is produced in the early stages of an infection and enters the nucleus and supports viral replication. HDAg-L, in contrast, is produced during the later stages of an infection, acts as an inhibitor of viral replication, and is required for assembly of viral particles.[25][26][27] Thus RNA editing by the cellular enzymes is critical to the virus’ life cycle because it regulates the balance between viral replication and virion assembly.


The routes of transmission of hepatitis D are similar to those for hepatitis B. Infection is largely restricted to persons at high risk of hepatitis B infection, particularly injecting drug users and persons receiving clotting factor concentrates. Worldwide more than 15 million people are co-infected. HDV is rare in most developed countries, and is mostly associated with intravenous drug use. However, HDV is much more common in the immediate Mediterranean region, sub-Saharan Africa, the Middle East, and the northern part of South America.[28] In all, about 20 million people may be infected with HDV.[29]

See also


  1. ^ Makino S, Chang MF, Shieh CK et al. (1987). "Molecular cloning and sequencing of a human hepatitis delta (delta) virus RNA". Nature 329 (6137): 343–6. doi:10.1038/329343a0. PMID 3627276. 
  2. ^ Fattovich G, Giustina G, Christensen E et al. (March 2000). "Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B". Gut 46 (3): 420–6. doi:10.1136/gut.46.3.420. PMC 1727859. PMID 10673308. http://gut.bmj.com/cgi/pmidlookup?view=long&pmid=10673308. 
  3. ^ Rizzetto, M; Canese MG, Arico S, Criello O, Trepo C, Bonino F, Verme G (1997). "Immunofluorescence detection of new antigen-antibody system (delta/anti-delta) associated to hepatitis B virus in liver and in serum of HBsAg carriers". Gut 18 (12): 997–1003. doi:10.1136/gut.18.12.997. PMC 1411847. PMID 75123. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1411847. 
  4. ^ Rizzetto, M; Canese, MG, Purcell, RH, London, WT, Sly, LD, Gerin, JL (1981 Nov-Dec). "Experimental HBV and delta infections of chimpanzees: occurrence and significance of intrahepatic immune complexes of HBcAg and delta antigen". Hepatology (Baltimore, Md.) 1 (6): 567–74. doi:10.1002/hep.1840010602. PMID 7030907. 
  5. ^ Wang, KS; Choo, QL, Weiner, AJ, Ou, JH, Najarian, RC, Thayer, RM, Mullenbach, GT, Denniston, KJ, Gerin, JL, Houghton, M (1986 Oct 9-15). "Structure, sequence and expression of the hepatitis delta (delta) viral genome". Nature 323 (6088): 508–14. doi:10.1038/323508a0. PMID 3762705. 
  6. ^ Fauquet, CM; Mayo MA, Maniloff J, Desselberger U, Ball LA (2005). "Deltavirus". Eight Report of the International Committee on Taxonomy of Viruses. London: 735–8. 
  7. ^ Poisson F, Roingeard P, Baillou A, Dubois F, Bonelli F, Calogero RA, Goudeau A (November 1993). "Characterization of RNA-binding domains of hepatitis delta antigen". J. Gen. Virol. 74 ( Pt 11): 2473-8. PMID 8245865. 
  8. ^ Zuccola HJ, Rozzelle JE, Lemon SM, Erickson BW, Hogle JM (July 1998). "Structural basis of the oligomerization of hepatitis delta antigen". Structure 6 (7): 821-30. PMID 9687364. 
  9. ^ Saldanha JA, Thomas HC, Monjardino JP (July 1990). "Cloning and sequencing of RNA of hepatitis delta virus isolated from human serum". J. Gen. Virol. 71 ( Pt 7) (7): 1603–6. doi:10.1099/0022-1317-71-7-1603. PMID 2374010. http://vir.sgmjournals.org/cgi/pmidlookup?view=long&pmid=2374010. 
  10. ^ Elena SF, Dopazo J, Flores R, Diener TO, Moya A (July 1991). "Phylogeny of viroids, viroidlike satellite RNAs, and the viroidlike domain of hepatitis delta virus RNA". Proc. Natl. Acad. Sci. U.S.A. 88 (13): 5631–4. doi:10.1073/pnas.88.13.5631. PMC 51931. PMID 1712103. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=1712103. 
  11. ^ Sureau, C (2006). "The role of the HBV envelope proteins in the HDV replication cycle". Current topics in microbiology and immunology. Current Topics in Microbiology and Immunology 307: 113–31. doi:10.1007/3-540-29802-9_6. ISBN 978-3-540-29801-4. PMID 16903223. 
  12. ^ Celik I, Karataylı E, Cevik E, Gökçe Kabakçı S, Karataylı SC, Dinç B, Cınar K, Yalçın K, Idilman R, Yurdaydın C, Bozdayi AM (2011) Complete genome sequences and phylogenetic analysis of hepatitis delta viruses isolated from nine Turkish patients. Arch Virol
  13. ^ Barrera, A; Guerra, B, Notvall, L, Lanford, RE (2005 Aug). "Mapping of the Hepatitis B Virus Pre-S1 Domain Involved in Receptor Recognition". Journal of virology 79 (15): 9786–98. doi:10.1128/JVI.79.15.9786-9798.2005. PMC 1181564. PMID 16014940. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1181564. 
  14. ^ Engelke, M; Mills, K, Seitz, S, Simon, P, Gripon, P, Schnölzer, M, Urban, S (2006 Apr). "Characterization of a hepatitis B and hepatitis delta virus receptor binding site". Hepatology (Baltimore, Md.) 43 (4): 750–60. doi:10.1002/hep.21112. PMID 16557545. 
  15. ^ Schulze, A; Schieck, A, Ni, Y, Mier, W, Urban, S (2010 Feb). "Fine Mapping of Pre-S Sequence Requirements for Hepatitis B Virus Large Envelope Protein-Mediated Receptor Interaction". Journal of virology 84 (4): 1989–2000. doi:10.1128/JVI.01902-09. PMC 2812397. PMID 20007265. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2812397. 
  16. ^ Xia, YP; Yeh, CT, Ou, JH, Lai, MM (1992 Feb). "Characterization of nuclear targeting signal of hepatitis delta antigen: nuclear transport as a protein complex". Journal of virology 66 (2): 914–21. PMC 240792. PMID 1731113. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=240792. 
  17. ^ Lehmann E, Brueckner F, Cramer P (November 2007). "Molecular basis of RNA-dependent RNA polymerase II activity". Nature 450 (7168): 445–9. doi:10.1038/nature06290. PMID 18004386. 
  18. ^ Filipovska J, Konarska MM (January 2000). "Specific HDV RNA-templated transcription by pol II in vitro". RNA 6 (1): 41–54. doi:10.1017/S1355838200991167. PMC 1369892. PMID 10668797. http://www.rnajournal.org/cgi/pmidlookup?view=long&pmid=10668797. 
  19. ^ Greco-Stewart, VS; Schissel, E, Pelchat, M (2009-03-30). "The hepatitis delta virus RNA genome interacts with the human RNA polymerases I and III". Virology 386 (1): 12–5. doi:10.1016/j.virol.2009.02.007. PMID 19246067. 
  20. ^ Li, YJ; Macnaughton, T, Gao, L, Lai, MM (2006 Jul). "RNA-Templated Replication of Hepatitis Delta Virus: Genomic and Antigenomic RNAs Associate with Different Nuclear Bodies". Journal of virology 80 (13): 6478–86. doi:10.1128/JVI.02650-05. PMC 1488965. PMID 16775335. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1488965. 
  21. ^ Branch, AD; Benenfeld, BJ, Baroudy, BM, Wells, FV, Gerin, JL, Robertson, HD (1989-02-03). "An ultraviolet-sensitive RNA structural element in a viroid-like domain of the hepatitis delta virus". Science 243 (4891): 649–52. doi:10.1126/science.2492676. PMID 2492676. 
  22. ^ Wu, HN; Lin, YJ, Lin, FP, Makino, S, Chang, MF, Lai, MM (1989 Mar). "Human hepatitis delta virus RNA subfragments contain an autocleavage activity". Proceedings of the National Academy of Sciences of the United States of America 86 (6): 1831–5. doi:10.1073/pnas.86.6.1831. PMC 286798. PMID 2648383. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=286798. 
  23. ^ a b Weiner, AJ; Choo, QL, Wang, KS, Govindarajan, S, Redeker, AG, Gerin, JL, Houghton, M (1988 Feb). "A single antigenomic open reading frame of the hepatitis delta virus encodes the epitope(s) of both hepatitis delta antigen polypeptides p24 delta and p27 delta". Journal of virology 62 (2): 594–9. PMC 250573. PMID 2447291. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=250573. 
  24. ^ Jayan, GC; Casey, JL (2002 Dec). "Inhibition of Hepatitis Delta Virus RNA Editing by Short Inhibitory RNA-Mediated Knockdown of ADAR1 but Not ADAR2 Expression". Journal of virology 76 (23): 12399–404. doi:10.1128/JVI.76.23.12399-12404.2002. PMC 136899. PMID 12414985. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=136899. 
  25. ^ Sato S, Cornillez-Ty C, Lazinski DW (August 2004). "By Inhibiting Replication, the Large Hepatitis Delta Antigen Can Indirectly Regulate Amber/W Editing and Its Own Expression". J. Virol. 78 (15): 8120–34. doi:10.1128/JVI.78.15.8120-8134.2004. PMC 446097. PMID 15254184. http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=15254184. 
  26. ^ Taylor, JM (2006). "Structure and replication of hepatitis delta virus RNA". Current topics in microbiology and immunology. Current Topics in Microbiology and Immunology 307: 1–23. doi:10.1007/3-540-29802-9_1. ISBN 978-3-540-29801-4. PMID 16903218. 
  27. ^ Chang, MF; Chen, CJ, Chang, SC (1994 Feb). "Mutational analysis of delta antigen: effect on assembly and replication of hepatitis delta virus". Journal of virology 68 (2): 646–53. PMC 236498. PMID 8289368. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=236498. 
  28. ^ Radjef N, Gordien E, Ivaniushina V et al. (March 2004). "Molecular Phylogenetic Analyses Indicate a Wide and Ancient Radiation of African Hepatitis Delta Virus, Suggesting a Deltavirus Genus of at Least Seven Major Clades". J. Virol. 78 (5): 2537–44. doi:10.1128/JVI.78.5.2537-2544.2004. PMC 369207. PMID 14963156. http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=14963156. 
  29. ^ Taylor JM (January 2006). "Hepatitis delta virus". Virology 344 (1): 71–6. doi:10.1016/j.virol.2005.09.033. PMID 16364738. 

External links

This article includes text from the public domain Pfam and InterPro IPR002506

Wikimedia Foundation. 2010.

Игры ⚽ Поможем написать курсовую

Look at other dictionaries:

  • Hepatitis C — Classification and external resources Electron micrograph of hepatitis C virus purified from cell culture. The scale = 50 nanometers ICD 10 B …   Wikipedia

  • Hepatitis B — Classification and external resources Electron micrograph of hepatitis B virus ICD 10 B …   Wikipedia

  • Hepatitis — Classification and external resources Alcoholic hepatitis evident by fatty change, cell necrosis, Mallory bodies ICD 10 K …   Wikipedia

  • Hepatitis B — Micrografía electrónica de un virus de la hepatitis B Clasificación y recursos externos CIE 10 …   Wikipedia Español

  • Hepatitis A — Clasificación y recursos externos CIE 10 B15 CIE 9 070.1 …   Wikipedia Español

  • Hepatitis C — Clasificación y recursos externos CIE 10 B …   Wikipedia Español

  • hepatitis — f. hepat. Inflamación aguda o crónica del hígado. Las causas pueden ser diversas: de tipo tóxico, tras la toma de ciertos fármacos, setas, alcohol y sustancias químicas como el tetracloruro de carbono; de tipo infeccioso, como la leptospirosis,… …   Diccionario médico

  • hepatitis B — bē n a sometimes fatal hepatitis caused by a double stranded DNA virus (species Hepatitis B virus of the genus Orthohepadnavirus, family Hepadnaviridae) that tends to persist in the blood serum and is transmitted esp. by contact with infected… …   Medical dictionary

  • hepatitis B — f. hepat. Hepatitis vírica que se transmite fundamentalmente a través de la sangre mediante transfusiones o con jeringas u objetos contaminados con ella. El período de incubación oscila entre 50 y 160 días. También se denomina hepatitis sérica.… …   Diccionario médico

  • hepatitis C — sē n hepatitis caused by a single stranded RNA virus of the family Flaviviridae (species Hepatitis C virus of the genus Hepacivirus) that tends to persist in the blood serum and is usu. transmitted by infected blood (as by injection of an illicit …   Medical dictionary

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”