Hepatitis D causes: Difference between revisions

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* Receiving many blood transfusions
* Receiving many blood transfusions


==Genome structure and similarities to viroids==
==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.<ref>{{cite journal |author=Saldanha JA, Thomas HC, Monjardino JP |title=Cloning and sequencing of RNA of hepatitis delta virus isolated from human serum |journal=J. Gen. Virol. |volume=71 ( Pt 7) |issue= |pages=1603–6 |year=1990 |month=July |pmid=2374010 |url=http://vir.sgmjournals.org/cgi/pmidlookup?view=long&pmid=2374010 |doi=10.1099/0022-1317-71-7-1603}}</ref> With a genome of approximately 1700 nucleotides, HDV is the smallest "virus" known to infect animals.  
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.<ref>{{cite journal |author=Saldanha JA, Thomas HC, Monjardino JP |title=Cloning and sequencing of RNA of hepatitis delta virus isolated from human serum |journal=J. Gen. Virol. |volume=71 ( Pt 7) |issue= |pages=1603–6 |year=1990 |month=July |pmid=2374010 |url=http://vir.sgmjournals.org/cgi/pmidlookup?view=long&pmid=2374010 |doi=10.1099/0022-1317-71-7-1603}}</ref> 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]].<ref>{{cite journal |author=Elena SF, Dopazo J, Flores R, Diener TO, Moya A |title=Phylogeny of viroids, viroidlike satellite RNAs, and the viroidlike domain of hepatitis delta virus RNA |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=88 |issue=13 |pages=5631–4 |year=1991 |month=July |pmid=1712103 |pmc=51931 |url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=1712103 |doi=10.1073/pnas.88.13.5631}}</ref> 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.<ref>{{cite journal |author=Taylor JM |title=Replication of human hepatitis delta virus: recent developments |journal=Trends Microbiol. |volume=11 |issue=4 |pages=185–90 |year=2003 |month=April |pmid=12706997 |doi=10.1016/S0966-842X(03)00045-3}}</ref> RNA polymerase II has been implicated as the polymerase responsible for the replication of HDV.<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> 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.
It has been proposed that HDV may have originated from a class of plant viruses called [[viroids]].<ref>{{cite journal |author=Elena SF, Dopazo J, Flores R, Diener TO, Moya A |title=Phylogeny of viroids, viroidlike satellite RNAs, and the viroidlike domain of hepatitis delta virus RNA |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=88 |issue=13 |pages=5631–4 |year=1991 |month=July |pmid=1712103 |pmc=51931 |url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=1712103 |doi=10.1073/pnas.88.13.5631}}</ref> 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.<ref>{{cite journal |author=Taylor JM |title=Replication of human hepatitis delta virus: recent developments |journal=Trends Microbiol. |volume=11 |issue=4 |pages=185–90 |year=2003 |month=April |pmid=12706997 |doi=10.1016/S0966-842X(03)00045-3}}</ref> RNA polymerase II has been implicated as the polymerase responsible for the replication of HDV.<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> 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 Delta Antigens==
===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.
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.
==References==
==References==

Revision as of 15:13, 9 February 2012

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Cause

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.[1] 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.[2] 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.[3] RNA polymerase II has been implicated as the polymerase responsible for the replication of HDV.[4][5] 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 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.

References

  1. 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)
  2. 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)
  3. 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)
  4. 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)
  5. 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)

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