Hepatitis D causes: Difference between revisions

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__NOTOC__
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{{Hepatitis D}}
{{Hepatitis D}}
{{CMG}}; {{AE}}
{{CMG}}; {{AE}} {{JS}} {{JM}}


==Overview==
==Overview==
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===Life Cycle===
===Life Cycle===
To replicate efficiently, a [[virus]] requires the cooperation of the host cell at all stages of the [[viral replication]] cycle:<ref name=WHO>{{cite web | title = Hepatitis D | url = http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf }}</ref>
To replicate efficiently, a [[virus]] requires the cooperation of the host cell at all stages of the [[viral replication]] cycle. These stages include:<ref name=WHO>{{cite web | title = Hepatitis D | url = http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf }}</ref>
#Attachment
#Attachment
#Penetration
#Penetration
#Uncoating
#Uncoating
#Provision of appropriate metabolic conditions for the synthesis of viral macromolecules
#Provision of appropriate [[metabolic]] conditions for the synthesis of [[viral]] macromolecules
#Final assembly of viral subunits
#Final assembly of viral subunits
#Release of new virions
#Release of new [[virions]]


*[[HDV]] also requires the presence of an helper [[hepadnavirus]] to provide the [[protein]] components for its own envelope. How HDV enters [[hepatocytes]] is still not known, but it may involve the interaction between HBsAg-L and a cellular receptor. The incoming [[HDV]] [[RNA]] is then transported into the [[nucleus]], probably by the small form of delta antigen, ''HDAg-S''. Binding of HDAg to RNA also protects the HDV RNAs from degradation.<ref name=WHO>{{cite web | title = Hepatitis D | url = http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf }}</ref>
[[Hepatitis D virus]] requires the presence of an helper [[hepadnavirus]] to provide the [[protein]] components for its own envelope. How [[HDV]] enters [[hepatocytes]] is still not known, but it may involve the interaction between ''HBsAg-L'' and a cellular receptor. The incoming [[HDV]] [[RNA]] is then transported into the [[nucleus]], probably by the small form of viral delta antigen, ''HDAg-S''. Binding of HDAg to [[RNA]] also protects the [[HDV]] [[RNA]]s from cellular degradation.<ref name=WHO>{{cite web | title = Hepatitis D | url = http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf }}</ref>


*HDV RNA replication is carried out by cellular [[RNA]] [[polymerase]] II, without a DNA intermediate, and without the help of HBV.
HDV RNA replication is carried out by cellular [[RNA]] [[polymerase]] II, without a DNA intermediate, and without the help of [[HBV]]. The RNA transcription is regulated.
*RNA transcription is regulated initially - [[mRNA]](s) is(are) transcribed from the incoming minus-strand genome
:*''Later'' - after the translation of the [[mRNA]] to make essential replication proteins, there is a switch in the mode of [[RNA]]-directed [[RNA synthesis]] to facilitate replication of the RNA [[genome]]
*Three forms of [[RNA]] are made:
*Three forms of [[RNA]] are made:
:*Circular [[genomic]] RNA
:*Circular [[genomic]] RNA
Line 47: Line 45:
:*[[RNA]]
:*[[RNA]]
These elements are only assembled in the presence of the [[hepatitis B virus]] (helper virus). [[HBsAg]] and HDAg-L are necessary and sufficient for [[virus]] assembly, whereas [[HDV]] RNA or HDAg-S are not required, but are present, in viral particles. The primary initiation event for [[HDV]] assembly is the interaction of HDAg-L with [[HBsAg]]. HDAg is localized in the [[nuclei]] while and [[HBsAg]] is present in the [[cytoplasm]] of the infected cells. The mechanism of interaction between these two proteins remains unknown. That are different models that try to explain the mechanisms of viral RNA transcription and replication.<ref name=WHO>{{cite web | title = Hepatitis D | url = http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf }}</ref><ref name="pmid9621000">{{cite journal| author=Modahl LE, Lai MM| title=Transcription of hepatitis delta antigen mRNA continues throughout hepatitis delta virus (HDV) replication: a new model of HDV RNA transcription and replication. | journal=J Virol | year= 1998 | volume= 72 | issue= 7 | pages= 5449-56 | pmid=9621000 | doi= | pmc=PMC110180 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9621000  }} </ref><ref>{{cite book | last = Fields | first = Bernard | title = Fields virology | publisher = Wolters Kluwer Health/Lippincott Williams & Wilkins | location = Philadelphia | year = 2013 | isbn = 1451105630 }}</ref>
These elements are only assembled in the presence of the [[hepatitis B virus]] (helper virus). [[HBsAg]] and HDAg-L are necessary and sufficient for [[virus]] assembly, whereas [[HDV]] RNA or HDAg-S are not required, but are present, in viral particles. The primary initiation event for [[HDV]] assembly is the interaction of HDAg-L with [[HBsAg]]. HDAg is localized in the [[nuclei]] while and [[HBsAg]] is present in the [[cytoplasm]] of the infected cells. The mechanism of interaction between these two proteins remains unknown. That are different models that try to explain the mechanisms of viral RNA transcription and replication.<ref name=WHO>{{cite web | title = Hepatitis D | url = http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf }}</ref><ref name="pmid9621000">{{cite journal| author=Modahl LE, Lai MM| title=Transcription of hepatitis delta antigen mRNA continues throughout hepatitis delta virus (HDV) replication: a new model of HDV RNA transcription and replication. | journal=J Virol | year= 1998 | volume= 72 | issue= 7 | pages= 5449-56 | pmid=9621000 | doi= | pmc=PMC110180 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9621000  }} </ref><ref>{{cite book | last = Fields | first = Bernard | title = Fields virology | publisher = Wolters Kluwer Health/Lippincott Williams & Wilkins | location = Philadelphia | year = 2013 | isbn = 1451105630 }}</ref>
<!--
'''The Delta Antigens'''
A significant difference between viroids and HDV is that, while viroids produce no proteins, HDV produces two proteins called the small and large delta antigens (HDAg-S and HDAg-L, respectively). These two proteins are produced from a single open reading frame. They are identical for 195 amino acids and differ only by the presence of an additional 19 amino acids at the C-terminus of HDAg-L. 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 is required for 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.
'''Evolution'''
Three genotypes (I-III) were originally described. Genotype I has been isolated in Europe, North America, Africa and some Asia. Genotype II has been found in Japan, Taiwan, and Yakutia (Russia). Genotype III has been found exclusively in South America (Peru, Colombia, and Venezuela). Some genomes from Taiwan and the Okinawa islands have been difficult to type but have been placed in genotype 2. However it is not known that 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>Phylogenetic studies suggest an African origin for this pathogen.<ref name=Radjef2004>Radjef N, Gordien E, Ivaniushina V, Gault E, Anaïs P, Drugan T, Trinchet JC, Roulot D, Tamby M, Milinkovitch MC, Dény P (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):2537-2544</ref>
-->


==Tropism==
==Tropism==


==Natural Reservoir==
==Natural Reservoir==
Humans are the only known [[natural reservoir]] of [[hepatitis D virus]], in nature. However, when in the presence of [[hepatitis B virus]], or woodchuck hepatitis virus, HDV can be experimentally transmitted to chimpanzees and woodchucks, respectively.<ref name="pmid7574482">{{cite journal| author=Lai MM| title=The molecular biology of hepatitis delta virus. | journal=Annu Rev Biochem | year= 1995 | volume= 64 | issue=  | pages= 259-86 | pmid=7574482 | doi=10.1146/annurev.bi.64.070195.001355 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7574482  }} </ref><ref name=WHO>{{cite web | title = Hepatitis D | url = http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf }}</ref><ref name="pmid2198992">{{cite journal| author=Monjardino JP, Saldanha JA| title=Delta hepatitis. The disease and the virus. | journal=Br Med Bull | year= 1990 | volume= 46 | issue= 2 | pages= 399-407 | pmid=2198992 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2198992  }} </ref>
Humans are the only known [[natural reservoir]] of [[hepatitis D virus]], in nature. However, when in the presence of [[hepatitis B virus]], or woodchuck hepatitis virus, HDV can be experimentally transmitted to chimpanzees and woodchucks, respectively.<ref name="pmid7574482">{{cite journal| author=Lai MM| title=The molecular biology of hepatitis delta virus. | journal=Annu Rev Biochem | year= 1995 | volume= 64 | issue=  | pages= 259-86 | pmid=7574482 | doi=10.1146/annurev.bi.64.070195.001355 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7574482  }} </ref><ref name=WHO>{{cite web | title = Hepatitis D | url = http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf }}</ref><ref name="pmid2198992">{{cite journal| author=Monjardino JP, Saldanha JA| title=Delta hepatitis. The disease and the virus. | journal=Br Med Bull | year= 1990 | volume= 46 | issue= 2 | pages= 399-407 | pmid=2198992 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2198992 }} </ref><ref name="pmid2778877">{{cite journal| author=Sureau C, Taylor J, Chao M, Eichberg JW, Lanford RE| title=Cloned hepatitis delta virus cDNA is infectious in the chimpanzee. | journal=J Virol | year= 1989 | volume= 63 | issue= 10 | pages= 4292-7 | pmid=2778877 | doi= | pmc=PMC251044 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2778877 }} </ref>


==References==
==References==
{{reflist|2}}
{{reflist|2}}

Revision as of 16:30, 5 August 2014

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2] Jolanta Marszalek, M.D. [3]

Overview

Taxonomy

Viruses; Deltavirus; Hepatitis delta virus

Biology

Electron micrograph revealing the presence of hepatitis-B virus HBV "Dane particles", or virions. Courtesy: World Health Organization[1]

The HDV genome is a single, negative stranded, circular RNA molecule nearly 1.7 kb in length containing about 60% C+G. A high degree of intramolecular complementarity allows about 70% of the nucleotides to be basepaired to each other to form an unbranched, double-stranded, stable, rod-shaped structure.[2][3] The genome of HDV is unrelated to the genomes of hepadnaviruses, of which hepatitis B virus (HBV) is a member.[4] HDV is a replication defective, helper (HBV) dependent ssRNA virus that requires the surface antigen of HBV (HBsAg) for the "encapsidation" of its own genome. The envelope proteins on the outer surface of HDV are entirely provided by HBV.[5][6]

The outer envelope of HDV particles contains lipids and the three forms (S, M, and L) of HBV surface antigen (HBsAg), but predominantly the major form of HBsAg with very few middle (pre S1) and large (pre S2) proteins. The internal nucleocapsid structure of HDV is composed of the viral single stranded RNA genome and about 60 copies of delta antigen, the only HDV-encoded protein.[5]

HDV does not infect established tissue culture cell lines. Complete viral replication cycles in vitro are limited to primary hepatocytes that are coinfected with a hepadnavirus or cotransfected with hepadnavirus cDNA.[5][2]

Life Cycle

To replicate efficiently, a virus requires the cooperation of the host cell at all stages of the viral replication cycle. These stages include:[5]

  1. Attachment
  2. Penetration
  3. Uncoating
  4. Provision of appropriate metabolic conditions for the synthesis of viral macromolecules
  5. Final assembly of viral subunits
  6. Release of new virions

Hepatitis D virus requires the presence of an helper hepadnavirus to provide the protein components for its own envelope. How HDV enters hepatocytes is still not known, but it may involve the interaction between HBsAg-L and a cellular receptor. The incoming HDV RNA is then transported into the nucleus, probably by the small form of viral delta antigen, HDAg-S. Binding of HDAg to RNA also protects the HDV RNAs from cellular degradation.[5]

HDV RNA replication is carried out by cellular RNA polymerase II, without a DNA intermediate, and without the help of HBV. The RNA transcription is regulated.

  • Three forms of RNA are made:
  • Circular genomic RNA
  • Circular complementary antigenomic RNA
  • Linear polyadenylated antigenomic RNA - mRNA containing the open reading frame for the HDAg.

Synthesis of antigenomic RNA occurs in the nucleous, mediated by RNA polymerase I, whereas synthesis of genomic RNA takes place in the nucleoplasm, mediated by RNA Pol II.[7]

  • Small (p24) form of HDAg (HDAg-S) - transactivator of HDV RNA replication
  • Large (p27) form of HDAg (HDAg-L) - inhibits RNA synthesis and initiates virion assembly with HBsAg.
  • HDV particles include:

These elements are only assembled in the presence of the hepatitis B virus (helper virus). HBsAg and HDAg-L are necessary and sufficient for virus assembly, whereas HDV RNA or HDAg-S are not required, but are present, in viral particles. The primary initiation event for HDV assembly is the interaction of HDAg-L with HBsAg. HDAg is localized in the nuclei while and HBsAg is present in the cytoplasm of the infected cells. The mechanism of interaction between these two proteins remains unknown. That are different models that try to explain the mechanisms of viral RNA transcription and replication.[5][10][11]

Tropism

Natural Reservoir

Humans are the only known natural reservoir of hepatitis D virus, in nature. However, when in the presence of hepatitis B virus, or woodchuck hepatitis virus, HDV can be experimentally transmitted to chimpanzees and woodchucks, respectively.[2][5][3][12]

References

  1. ↑ "http://www.who.int/en/". External link in |title= (help)
  2. ↑ 2.0 2.1 2.2 2.3 Lai MM (1995). "The molecular biology of hepatitis delta virus". Annu Rev Biochem. 64: 259–86. doi:10.1146/annurev.bi.64.070195.001355. PMID 7574482.
  3. ↑ 3.0 3.1 Monjardino JP, Saldanha JA (1990). "Delta hepatitis. The disease and the virus". Br Med Bull. 46 (2): 399–407. PMID 2198992.
  4. ↑ Nakamura A, Osonoi T, Terauchi Y (2010). "Relationship between urinary sodium excretion and pioglitazone-induced edema". J Diabetes Investig. 1 (5): 208–11. doi:10.1111/j.2040-1124.2010.00046.x. PMC 4020723. PMID 24843434.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 "Hepatitis D" (PDF).
  6. ↑ Makino S, Chang MF, Shieh CK, Kamahora T, Vannier DM, Govindarajan S; 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.
  7. ↑ 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. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  8. ↑ Dingle K, Bichko V, Zuccola H, Hogle J, Taylor J (1998). "Initiation of hepatitis delta virus genome replication". J Virol. 72 (6): 4783–8. PMC 110015. PMID 9573243.
  9. ↑ Ryu WS, Bayer M, Taylor J (1992). "Assembly of hepatitis delta virus particles". J Virol. 66 (4): 2310–5. PMC 289026. PMID 1548764.
  10. ↑ Modahl LE, Lai MM (1998). "Transcription of hepatitis delta antigen mRNA continues throughout hepatitis delta virus (HDV) replication: a new model of HDV RNA transcription and replication". J Virol. 72 (7): 5449–56. PMC 110180. PMID 9621000.
  11. ↑ Fields, Bernard (2013). Fields virology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 1451105630.
  12. ↑ Sureau C, Taylor J, Chao M, Eichberg JW, Lanford RE (1989). "Cloned hepatitis delta virus cDNA is infectious in the chimpanzee". J Virol. 63 (10): 4292–7. PMC 251044. PMID 2778877.
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