Hepatitis D pathophysiology
|
Hepatitis D |
|
Diagnosis |
|
Treatment |
|
Hepatitis D pathophysiology On the Web |
|
American Roentgen Ray Society Images of Hepatitis D pathophysiology |
|
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
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.[1] HDV recognizes its receptor via the N-terminal domain of the large hepatitis B surface antigen, HBsAg.[2] Mapping by mutagenesis of this domain has shown that aminoacid residues 9-15 make up the receptor binding site.[3] After entering the hepatocyte, the virus is uncoated and the nucleocapsid translocated to the nucleus due to a signal in HDAg[4] 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,[5][6] now RNA polymerases I and III have also been shown to be involved in HDV replication[7] 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.[8] 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 [9][10]
There are eight reported genotypes of HDV with unexplained variations in their geographical distribution and pathogenicity.
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
{{#ev:youtube|_hXvbpSxFZw}}
References
- ↑ 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. Unknown parameter
|coauthors=ignored (help); Check date values in:|date=(help) - ↑ 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. Unknown parameter
|coauthors=ignored (help); Check date values in:|date=(help) - ↑ 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. Unknown parameter
|coauthors=ignored (help); Check date values in:|date=(help) - ↑ 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. Unknown parameter
|coauthors=ignored (help); Check date values in:|date=(help) - ↑ 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. Unknown parameter
|month=ignored (help) - ↑ 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. Unknown parameter
|month=ignored (help) - ↑ 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. Unknown parameter
|coauthors=ignored (help) - ↑ 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) - ↑ 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. Unknown parameter
|coauthors=ignored (help) - ↑ 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. Unknown parameter
|coauthors=ignored (help); Check date values in:|date=(help)