Hepatitis D causes: Difference between revisions
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*[[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.<ref name=WHO>{{cite web | title = Hepatitis D | url = http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf }}</ref> | *[[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.<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. | ||
*RNA transcription is regulated: | *RNA transcription is regulated:<ref name=WHO>{{cite web | title = Hepatitis D | url = http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf }}</ref> | ||
:*Initially - mRNA(s) is(are) transcribed from the incoming minus-strand genome | :*''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]] | :*''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]] | ||
*Translation of the 800 b RNA transcript yields: | *Translation of the 800 b RNA transcript yields:<ref name=WHO>{{cite web | title = Hepatitis D | url = http://www.who.int/csr/disease/hepatitis/HepatitisD_whocdscsrncs2001_1.pdf }}</ref> | ||
:*Small (p24) form of HDAg (HDAg-S) - transactivator of HDV RNA replication | :*''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 | :*''Large (p27) form of HDAg (HDAg-L)'' - inhibits [[RNA synthesis]] and initiates [[virion]] assembly with HBsAg | ||
Revision as of 15:57, 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 causes On the Web |
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American Roentgen Ray Society Images of Hepatitis D causes |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Varun Kumar, M.B.B.S. [2];
Overview
Taxonomy
Viruses; Deltavirus; Hepatitis delta virus
Biology
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Causes
Hepatitis D virus(HDV) is the causative organism for Hepatitis D infection. HDV is only found in people who carry the hepatitis B virus. HDV may make a recent (acute) hepatitis B infection or an existing long-term (chronic) hepatitis B liver disease worse. It can even cause symptoms in people who carry hepatitis B virus but who never had symptoms. Hepatitis D infects about 15 million people worldwide. It occurs in 5% of people who carry hepatitis B. Risk factors include:
- Abusing intravenous (IV) or injection drugs
- Being infected while pregnant (the mother can pass the virus to the baby)
- Carrying the hepatitis B virus
- Men having sexual intercourse with other men
- Receiving many blood transfusions
Virology
Genome structure and similarities to viroids
The HDV genome exists as a negative sense, single-stranded, closed circular RNA. Because of a nucleotide sequence that is 70% self-complementary, the HDV genome forms a partially double stranded RNA structure that is described as rod-like.[2] 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.[3] Evidence in support of this hypothesis stems from the fact that both HDV and viroids exist as single-stranded, closed circular RNAs that have rod-like structures. Likewise, both HDV and viroids contain RNA sequences that can assume catalytically active structures called ribozymes. During viral replication, these catalytic RNAs are required in order to produce unit length copies of the genome from longer RNA concatamers. Finally, neither HDV nor viroids encode their own polymerase. Instead, replication of HDV and viroids requires a host polymerase that can utilize RNA as a template.[4] RNA polymerase II has been implicated as the polymerase responsible for the replication of HDV.[5][6] 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.
Life Cycle
To replicate efficiently, a virus requires the cooperation of the host cell at all stages of the replicative cycle:[7]
- 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.[7]
- 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:[7]
- 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
- Translation of the 800 b RNA transcript yields:[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
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).[8]Phylogenetic studies suggest an African origin for this pathogen.[9]
References
- ↑ "http://www.who.int/en/". External link in
|title=(help) - ↑ Saldanha JA, Thomas HC, Monjardino JP (1990). "Cloning and sequencing of RNA of hepatitis delta virus isolated from human serum". J. Gen. Virol. 71 ( Pt 7): 1603–6. doi:10.1099/0022-1317-71-7-1603. PMID 2374010. Unknown parameter
|month=ignored (help) - ↑ 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. Unknown parameter
|month=ignored (help) - ↑ Taylor JM (2003). "Replication of human hepatitis delta virus: recent developments". Trends Microbiol. 11 (4): 185–90. doi:10.1016/S0966-842X(03)00045-3. PMID 12706997. Unknown parameter
|month=ignored (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) - ↑ 7.0 7.1 7.2 7.3 "Hepatitis D" (PDF).
- ↑ 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. Unknown parameter
|month=ignored (help) - ↑ 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