Hepatitis D pathophysiology: Difference between revisions
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#Final assembly of viral subunits | #Final assembly of viral subunits | ||
#Release of new virions | #Release of new virions | ||
[[HDV]] also requires the presence of a 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. | [[HDV]] also requires the presence of a 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. | ||
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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.<ref>{{cite journal|last=Barrera|first=A|coauthors=Guerra, B, Notvall, L, Lanford, RE|title=Mapping of the Hepatitis B Virus Pre-S1 Domain Involved in Receptor Recognition|journal=Journal of virology|date=2005 Aug|volume=79|issue=15|pages=9786–98|pmid=16014940|doi=10.1128/JVI.79.15.9786-9798.2005|pmc=1181564}}</ref> HDV recognizes its receptor via the N-terminal domain of the large hepatitis B surface antigen, HBsAg.<ref>{{cite journal|last=Engelke|first=M|coauthors=Mills, K, Seitz, S, Simon, P, Gripon, P, Schnölzer, M, Urban, S|title=Characterization of a hepatitis B and hepatitis delta virus receptor binding site|journal=Hepatology (Baltimore, Md.)|date=2006 Apr|volume=43|issue=4|pages=750–60|pmid=16557545|doi=10.1002/hep.21112}}</ref> Mapping by mutagenesis of this domain has shown that aminoacid residues 9-15 make up the receptor binding site.<ref>{{cite journal|last=Schulze|first=A|coauthors=Schieck, A, Ni, Y, Mier, W, Urban, S|title=Fine Mapping of Pre-S Sequence Requirements for Hepatitis B Virus Large Envelope Protein-Mediated Receptor Interaction|journal=Journal of virology|date=2010 Feb|volume=84|issue=4|pages=1989–2000|pmid=20007265|doi=10.1128/JVI.01902-09|pmc=2812397}}</ref> After entering the hepatocyte, the virus is uncoated and the nucleocapsid translocated to the nucleus due to a signal in HDAg<ref>{{cite journal|last=Xia|first=YP|coauthors=Yeh, CT, Ou, JH, Lai, MM|title=Characterization of nuclear targeting signal of hepatitis delta antigen: nuclear transport as a protein complex|journal=Journal of virology|date=1992 Feb|volume=66|issue=2|pages=914–21|pmid=1731113|pmc=240792}}</ref> 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,<ref>{{cite journal|author=Lehmann E, Brueckner F, Cramer P|title=Molecular basis of RNA-dependent RNA polymerase II activity|journal=Nature|volume=450|issue=7168|pages=445–9|year=2007|month=November|pmid=18004386|doi=10.1038/nature06290}}</ref><ref>{{cite journal|author=Filipovska J, Konarska MM|title=Specific HDV RNA-templated transcription by pol II in vitro|journal=RNA|volume=6|issue=1|pages=41–54|year=2000|month=January|pmid=10668797|pmc=1369892|url=http://www.rnajournal.org/cgi/pmidlookup?view=long&pmid=10668797|doi=10.1017/S1355838200991167}}</ref> now RNA polymerases I and III have also been shown to be involved in HDV replication<ref>{{cite journal|last=Greco-Stewart|first=VS|coauthors=Schissel, E, Pelchat, M|title=The hepatitis delta virus RNA genome interacts with the human RNA polymerases I and III|journal=Virology|date=2009-03-30|volume=386|issue=1|pages=12–5|pmid=19246067|doi=10.1016/j.virol.2009.02.007}}</ref> | 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.<ref>{{cite journal|last=Barrera|first=A|coauthors=Guerra, B, Notvall, L, Lanford, RE|title=Mapping of the Hepatitis B Virus Pre-S1 Domain Involved in Receptor Recognition|journal=Journal of virology|date=2005 Aug|volume=79|issue=15|pages=9786–98|pmid=16014940|doi=10.1128/JVI.79.15.9786-9798.2005|pmc=1181564}}</ref> HDV recognizes its receptor via the N-terminal domain of the large hepatitis B surface antigen, HBsAg.<ref>{{cite journal|last=Engelke|first=M|coauthors=Mills, K, Seitz, S, Simon, P, Gripon, P, Schnölzer, M, Urban, S|title=Characterization of a hepatitis B and hepatitis delta virus receptor binding site|journal=Hepatology (Baltimore, Md.)|date=2006 Apr|volume=43|issue=4|pages=750–60|pmid=16557545|doi=10.1002/hep.21112}}</ref> Mapping by mutagenesis of this domain has shown that aminoacid residues 9-15 make up the receptor binding site.<ref>{{cite journal|last=Schulze|first=A|coauthors=Schieck, A, Ni, Y, Mier, W, Urban, S|title=Fine Mapping of Pre-S Sequence Requirements for Hepatitis B Virus Large Envelope Protein-Mediated Receptor Interaction|journal=Journal of virology|date=2010 Feb|volume=84|issue=4|pages=1989–2000|pmid=20007265|doi=10.1128/JVI.01902-09|pmc=2812397}}</ref> After entering the hepatocyte, the virus is uncoated and the nucleocapsid translocated to the nucleus due to a signal in HDAg<ref>{{cite journal|last=Xia|first=YP|coauthors=Yeh, CT, Ou, JH, Lai, MM|title=Characterization of nuclear targeting signal of hepatitis delta antigen: nuclear transport as a protein complex|journal=Journal of virology|date=1992 Feb|volume=66|issue=2|pages=914–21|pmid=1731113|pmc=240792}}</ref> 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,<ref>{{cite journal|author=Lehmann E, Brueckner F, Cramer P|title=Molecular basis of RNA-dependent RNA polymerase II activity|journal=Nature|volume=450|issue=7168|pages=445–9|year=2007|month=November|pmid=18004386|doi=10.1038/nature06290}}</ref><ref>{{cite journal|author=Filipovska J, Konarska MM|title=Specific HDV RNA-templated transcription by pol II in vitro|journal=RNA|volume=6|issue=1|pages=41–54|year=2000|month=January|pmid=10668797|pmc=1369892|url=http://www.rnajournal.org/cgi/pmidlookup?view=long&pmid=10668797|doi=10.1017/S1355838200991167}}</ref> now RNA polymerases I and III have also been shown to be involved in HDV replication<ref>{{cite journal|last=Greco-Stewart|first=VS|coauthors=Schissel, E, Pelchat, M|title=The hepatitis delta virus RNA genome interacts with the human RNA polymerases I and III|journal=Virology|date=2009-03-30|volume=386|issue=1|pages=12–5|pmid=19246067|doi=10.1016/j.virol.2009.02.007}}</ref> | ||
Revision as of 12:22, 4 August 2014
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Hepatitis D |
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Diagnosis |
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Treatment |
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Hepatitis D pathophysiology On the Web |
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American Roentgen Ray Society Images of Hepatitis D pathophysiology |
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Risk calculators and risk factors for Hepatitis D pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Varun Kumar, M.B.B.S. [2]; João André Alves Silva, M.D. [3] Jolanta Marszalek, M.D. [4]
Overview
Pathogenesis
Life Cycle
To replicate efficiently, a virus requires the cooperation of the host cell at all stages of the replicative cycle:
- Attachment
- Penetration
- Uncoating
- Provision of appropriate metabolic conditions for the synthesis of viral macromolecules
- Final assembly of viral subunits
- Release of new virions
HDV also requires the presence of a 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.
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.
Transmission is similar to that of HBV:
- Bloodborne and sexual
- Percutaneous (IV drug use, haemophiliacs)
- Permucosal (sexual)
- Perinatal (rare)
HDV is transmitted percutaneously or sexually through contact with infected blood or blood products.
Blood is potentially infectious during all phases of active hepatitis D infection. Peak infectivity probably occurs just before the onset of acute disease.
Associated Conditions
Macroscopic Pathology
Microscopic Pathology
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