Hepatitis D

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style="background:#Template:Taxobox colour;"|Template:Taxobox name
style="background:#Template:Taxobox colour;" | Virus classification
Group: Group V ((-)ssRNA)
Genus: Deltavirus
Species: Hepatitis delta virus

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

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Overview

Hepatitis D is a disease caused by a small circular RNA virus (Hepatitis delta virus or hepatitis D virus, HDV). HDV is considered to be a subviral satellite because it can propagate only in the presence of another virus, the hepatitis B virus (HBV). Transmission of HDV can occur either via simultaneous infection with HBV (coinfection) or via infection of an individual previously infected with HBV (superinfection).

Both superinfection and coinfection with HDV results in more severe complications compared to infection with HBV alone. These complications include a greater likelihood of experiencing liver failure in acute infections and a greater likelihood of developing liver cancer in chronic infections. In combination with hepatitis B virus, hepatitis D has the highest mortality rate of all the hepatitis infections of 20%.

Incidence

HDV is rare in most developed countries, and is mostly associated with intravenous drug abuse. However HDV is much more common in Mediterranean countries, sub-Saharan Africa, the Middle East, and countries in the northern part of South America.[1] In all, about 20 million people may be infected with HDV.[2]

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.[3] 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.[4] 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.[5] RNA polymerase II has been implicated as the polymerase responsible for the replication of HDV.[6][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 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.

Risk Factors

  • Injection drug users
  • Men who have sex with men
  • Hemodialysis patients
  • Sex contacts of infected persons

Health care and public safety workers Infants born to infected mothers (very rare) [3]

Pathophysiology & Etiology

Hepatitis D is a liver disease caused by the hepatitis D virus (HDV), a defective virus that needs the hepatitis B virus to exist. Hepatitis D virus (HDV) is found in the blood of persons infected with the virus.

  • Occurs when blood from an infected person enters the body of a person who is not immune.
  • HBV is spread through having sex with an infected person without using a condom (the efficacy of latex condoms in preventing infection with HBV is unknown, but their proper use may reduce transmission);
  • By sharing drugs, needles, or "works" when "shooting" drugs;
  • Through needlesticks or sharps exposures on the job; or
  • From an infected mother to her baby during birth.[4] [5]

History and Symptoms

Prevention

  • Prompt recognition and treatment of hepatitis B infection can help prevent hepatitis D.
  • Avoid intravenous drug abuse. If you use IV drugs, avoid sharing needles.
  • A vaccine is available to prevent hepatitis B. It should be considered by people who are at high risk for hepatitis B infection.

References

  1. Radjef N, Gordien E, Ivaniushina V; et al. (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): 2537–44. doi:10.1128/JVI.78.5.2537-2544.2004. PMC 369207. PMID 14963156. Unknown parameter |month= ignored (help)
  2. Taylor JM (2006). "Hepatitis delta virus". Virology. 344 (1): 71–6. doi:10.1016/j.virol.2005.09.033. PMID 16364738. Unknown parameter |month= ignored (help)
  3. 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)
  4. 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)
  5. 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)
  6. 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)
  7. 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)

See also

External links


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