Hepatitis D causes: Difference between revisions
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==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, | 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 experimentaly transmitted to chimpanzees and woodchucks, respectively. | ||
==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} |
Revision as of 16:11, 5 August 2014
Hepatitis D |
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Hepatitis D causes On the Web |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Taxonomy
Viruses; Deltavirus; Hepatitis delta virus
Biology
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:[5]
- 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 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.[5]
- HDV RNA replication is carried out by cellular RNA polymerase II, without a DNA intermediate, and without the help of HBV.
- 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:
- 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 experimentaly transmitted to chimpanzees and woodchucks, respectively.
References
- ↑ "http://www.who.int/en/". External link in
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(help) - ↑ 2.0 2.1 2.2 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.
- ↑ Monjardino JP, Saldanha JA (1990). "Delta hepatitis. The disease and the virus". Br Med Bull. 46 (2): 399–407. PMID 2198992.
- ↑ 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.
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 "Hepatitis D" (PDF).
- ↑ 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.
- ↑ 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
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(help) - ↑ 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.
- ↑ Ryu WS, Bayer M, Taylor J (1992). "Assembly of hepatitis delta virus particles". J Virol. 66 (4): 2310–5. PMC 289026. PMID 1548764.
- ↑ 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.
- ↑ Fields, Bernard (2013). Fields virology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 1451105630.