Hepatitis D: Difference between revisions

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The HDV is a small, spherical virus with a 36&nbsp;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.<ref name="pmid8245865">{{cite journal | author = Poisson F, Roingeard P, Baillou A, Dubois F, Bonelli F, Calogero RA, Goudeau A | title = Characterization of RNA-binding domains of hepatitis delta antigen | journal = J. Gen. Virol. | volume = 74 ( Pt 11) | issue = | pages = 2473–8 | year = 1993 | month = November | pmid = 8245865 | doi = | url = }}</ref> Several interactions are also mediated by a [[coiled coil|coiled-coil]] region at the [[N terminus]] of HDAg.<ref name="pmid9687364">{{cite journal | author = Zuccola HJ, Rozzelle JE, Lemon SM, Erickson BW, Hogle JM | title = Structural basis of the oligomerization of hepatitis delta antigen | journal = Structure | volume = 6 | issue = 7 | pages = 821–30 | year = 1998 | month = July | pmid = 9687364 | doi = 10.1016/S0969-2126(98)00084-7| url = }}</ref> 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.<ref>{{cite journal|author=Saldanha JA, Thomas HC, Monjardino JP|title=Cloning and sequencing of RNA of hepatitis delta virus isolated from human serum|journal=J. Gen. Virol.|volume=71 ( Pt 7)|issue=7|pages=1603–6|year=1990|month=July|pmid=2374010|url=http://vir.sgmjournals.org/cgi/pmidlookup?view=long&pmid=2374010|doi=10.1099/0022-1317-71-7-1603}}</ref> 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]].<ref>{{cite journal|author=Elena SF, Dopazo J, Flores R, Diener TO, Moya A|title=Phylogeny of viroids, viroidlike satellite RNAs, and the viroidlike domain of hepatitis delta virus RNA|journal=Proc. Natl. Acad. Sci. U.S.A.|volume=88|issue=13|pages=5631–4|year=1991|month=July|pmid=1712103|pmc=51931|url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=1712103|doi=10.1073/pnas.88.13.5631}}</ref><ref>{{cite journal|last=Sureau|first=C|title=The role of the HBV envelope proteins in the HDV replication cycle|journal=Current topics in microbiology and immunology|year=2006|volume=307|pages=113–31|pmid=16903223|doi=10.1007/3-540-29802-9_6|series=Current Topics in Microbiology and Immunology|isbn=978-3-540-29801-4}}</ref>
The HDV is a small, spherical virus with a 36&nbsp;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.<ref name="pmid8245865">{{cite journal | author = Poisson F, Roingeard P, Baillou A, Dubois F, Bonelli F, Calogero RA, Goudeau A | title = Characterization of RNA-binding domains of hepatitis delta antigen | journal = J. Gen. Virol. | volume = 74 | issue =Pt 11 | pages = 2473–8 | year = 1993 | month = November | pmid = 8245865 }}</ref> Several interactions are also mediated by a [[coiled coil|coiled-coil]] region at the [[N terminus]] of HDAg.<ref name="pmid9687364">{{cite journal | author = Zuccola HJ, Rozzelle JE, Lemon SM, Erickson BW, Hogle JM | title = Structural basis of the oligomerization of hepatitis delta antigen | journal = Structure | volume = 6 | issue = 7 | pages = 821–30 | year = 1998 | month = July | pmid = 9687364 | doi = 10.1016/S0969-2126(98)00084-7}}</ref> 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.<ref>{{cite journal|author=Saldanha JA, Thomas HC, Monjardino JP|title=Cloning and sequencing of RNA of hepatitis delta virus isolated from human serum|journal=J. Gen. Virol.|volume=71 |issue=7|pages=1603–6|year=1990|month=July|pmid=2374010|url=http://vir.sgmjournals.org/cgi/pmidlookup?view=long&pmid=2374010|doi=10.1099/0022-1317-71-7-1603}}</ref> 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]].<ref>{{cite journal|author=Elena SF, Dopazo J, Flores R, Diener TO, Moya A|title=Phylogeny of viroids, viroidlike satellite RNAs, and the viroidlike domain of hepatitis delta virus RNA|journal=Proc. Natl. Acad. Sci. U.S.A.|volume=88|issue=13|pages=5631–4|year=1991|month=July|pmid=1712103|pmc=51931|url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=1712103|doi=10.1073/pnas.88.13.5631}}</ref><ref>{{cite journal|last=Sureau|first=C|title=The role of the HBV envelope proteins in the HDV replication cycle|journal=Current topics in microbiology and immunology|year=2006|volume=307|pages=113–31|pmid=16903223|doi=10.1007/3-540-29802-9_6|series=Current Topics in Microbiology and Immunology|isbn=978-3-540-29801-4}}</ref>


There are at least 8 genotypes of this virus (HDV-1 to HDV-8).<ref name=Celik2011>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 </ref>
There are at least 8 genotypes of this virus (HDV-1 to HDV-8).<ref name=Celik2011>{{cite journal |author=Celik I, Karataylı E, Cevik E, ''et al.'' |title=Complete genome sequences and phylogenetic analysis of hepatitis delta viruses isolated from nine Turkish patients |journal=Arch. Virol. |volume=156 |issue=12 |pages=2215–20 |year=2011 |month=December |pmid=21984217 |doi=10.1007/s00705-011-1120-y }}</ref>


===Life Cycle===
===Life Cycle===

Revision as of 10:03, 14 December 2011

Hepatitis D
Virus classification
Group:
Group V ((−)ssRNA)
Order:
Unassigned
Family:
Unassigned
Genus:
Deltavirus
Species:
Hepatitis delta virus
Hepatitis D
SpecialtyInfectious diseases Edit this on Wikidata

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%.

Virology

History

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
oligomerization domain of hepatitis delta antigen
Identifiers
SymbolHDV_ag
PfamPF01517
InterProIPR002506
SCOP21a92 / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

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.

Transmission

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

References

  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. {{cite journal}}: Unknown parameter |author-separator= ignored (help)
  2. ^ Fattovich G; Giustina G; Christensen E; et al. (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. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  3. ^ Rizzetto, M (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. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  4. ^ Rizzetto, M (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. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: date and year (link)
  5. ^ Wang, KS (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. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: date and year (link)
  6. ^ Fauquet, CM (2005). "Deltavirus". Eight Report of the International Committee on Taxonomy of Viruses. London: 735–8. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  7. ^ Poisson F, Roingeard P, Baillou A, Dubois F, Bonelli F, Calogero RA, Goudeau A (1993). "Characterization of RNA-binding domains of hepatitis delta antigen". J. Gen. Virol. 74 (Pt 11): 2473–8. PMID 8245865. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  8. ^ Zuccola HJ, Rozzelle JE, Lemon SM, Erickson BW, Hogle JM (1998). "Structural basis of the oligomerization of hepatitis delta antigen". Structure. 6 (7): 821–30. doi:10.1016/S0969-2126(98)00084-7. PMID 9687364. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  9. ^ Saldanha JA, Thomas HC, Monjardino JP (1990). "Cloning and sequencing of RNA of hepatitis delta virus isolated from human serum". J. Gen. Virol. 71 (7): 1603–6. doi:10.1099/0022-1317-71-7-1603. PMID 2374010. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  10. ^ Elena SF, Dopazo J, Flores R, Diener TO, Moya A (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  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; et al. (2011). "Complete genome sequences and phylogenetic analysis of hepatitis delta viruses isolated from nine Turkish patients". Arch. Virol. 156 (12): 2215–20. doi:10.1007/s00705-011-1120-y. PMID 21984217. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  13. ^ Barrera, A (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. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  14. ^ Engelke, M (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. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  15. ^ Schulze, A (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. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  16. ^ Xia, YP (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. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  17. ^ Lehmann E, Brueckner F, Cramer P (2007). "Molecular basis of RNA-dependent RNA polymerase II activity". Nature. 450 (7168): 445–9. doi:10.1038/nature06290. PMID 18004386. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  18. ^ Filipovska J, Konarska MM (2000). "Specific HDV RNA-templated transcription by pol II in vitro". RNA. 6 (1): 41–54. doi:10.1017/S1355838200991167. PMC 1369892. PMID 10668797. {{cite journal}}: Unknown parameter |month= ignored (help)
  19. ^ Greco-Stewart, VS (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. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  20. ^ Li, YJ (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. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  21. ^ Branch, AD (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. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  22. ^ Wu, HN (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. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  23. ^ a b Weiner, AJ (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. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  24. ^ Jayan, GC (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. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  25. ^ Sato S, Cornillez-Ty C, Lazinski DW (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  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 (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. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  28. ^ Radjef N; Gordien E; Ivaniushina V; et al. (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. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  29. ^ Taylor JM (2006). "Hepatitis delta virus". Virology. 344 (1): 71–6. doi:10.1016/j.virol.2005.09.033. PMID 16364738. {{cite journal}}: Unknown parameter |month= ignored (help)

External links

This article incorporates text from the public domain Pfam and InterPro: IPR002506
Retrieved from "https://en.wikipedia.org/w/index.php?title=Hepatitis_D&oldid=465791442"