Hepatitis Delta Virus

Abstract

Several viruses are important causes of acute and chronic infections of the human liver. (HDV) is a most unusual agent that is found only in association with . HDV can make HBV infections more damaging to the liver. HDV needs the envelope proteins of HBV to achieve virus assembly and infection of new susceptible cells. Thus, HDV infections can be prevented with the vaccine against HBV envelope proteins. HDV has an RNA genome that is unique in that it is very small (around 1700 nucleotides) and has a circular conformation. This genome is replicated via redirection of host RNA polymerase activity to act on RNA templates. This replication is fundamentally different from that of HBV, which involves reverse transcription.

Key Concepts

  • HDV is unlike any other animal virus.
  • HDV has similarities and yet distinct differences from viroids, agents that infect plants.
  • HDV only encodes one protein and yet by RNA editing creates an essential second protein.
  • HDV replicates by redirecting host RNA polymerase activity.
  • HDV can make HBV infections more pathogenic.

Keywords: hepatitis; delta; virus; interferon; ribozymes; RNA transcription; RNA editing

Figure 1. The three RNAs detected during the replication of HDV. (a) The first is the 1679‐nt single‐stranded circular RNA found within virions, and thus defined as the genome. (b) The second is an exact complement of the genome, defined as the antigenome, and together with the genome, it is found in the nuclei of infected cells. (c) A third RNA, the least abundant, cytoplasmic, about 800 nt in length, 5′‐capped and 3′‐polyadenylated, is the messenger RNA for the translation of the delta protein. Note that both the genome and the antigenome are drawn as having an unbranched rod‐like structure, involving extensive (around 74%) predicted level of intra‐molecular base‐pairing. Also, each contains a domain, with an alternative folding, that will act as a self‐cleaving ribozyme. Adapted from Taylor (2005), with permission, © Oxford University Press.
close

References

Alves C, Cheng H, Roder H and Taylor J (2010) Intrinsic disorder and oligomerization of the hepatitis delta virus antigen. Virology 407: 333–340.

Bordier BB, Ohkanda J, Liu P, Lee S‐Y, et al. (2003) In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus. Journal of Clinical Investigation 112: 407–414.

Chang J, Nie X, Gudima S and Taylor J (2006) Action of inhibitors on accumulation of processed hepatitis delta virus RNAs. Journal of Virology 80: 3205–3214.

Deny, P. (2006) Hepatitis delta virus genetic variability: from genotypes I, II, III to eight major clades. Casey, J. (2006). Hepatitis Delta Virus. 151–171. Heidelberg, Germany: Springer.

Farci P (2012) Clinical features of hepatitis D. Seminars in Liver Disease 32: 228–236.

Flores R, Ruiz‐Ruiz S and Sera P (2012) Viroids and hepatitis delta virus. Seminars in Liver Disease 32: 201–210.

Gaeta GB, Stroffolini T, Chiaramonte M, et al. (2000) Chronic hepatitis D: a vanishing disease? An Italian multicenter study. Hepatology 32: 824–827.

Gowans EJ and Bonino F (1993) Hepatitis delta virus pathogenicity. Progress in Clinical and Biological Research 382: 125–130.

Hughes SA, Wedemeyer H, and Harrison PM (2011) Hepatitis delta virus. Lancet 378: 73–85.

Kapral GJ, Jain S, Noeske J et al., (2014) New tools provide a second look at HBV ribozyme structure, dynamics and cleavage. Nucleic Acids Research 42: 12833–12846.

Macnaughton TB, Shi ST, Modahl LE and Lai MMC (2002) Rolling circle replication of hepatitis delta virus RNA is carried out by two different cellular RNA polymerases. Journal of Virology 76: 3920–3927.

Niro GA, Rosino F and Rizzetto M (2005) Treatment of hepatitis D. Journal of Viral Hepatitis 12: 2–9.

Polson AG, Ley HL III, Bass BL and Casey JL (1998) Hepatitis delta virus RNA editing is highly specific for the amber/W site and is suppressed by hepatitis delta antigen. Molecular and Cellular Biology 18: 1919–1926.

Radjef N, Gordien E, Ivaniusha V, et al. (2004) Journal of Virology 78: 2537–2544.

Sato S, Wong SK and Lazinski DW (2001) Hepatitis delta virus minimal substrates competent for editing by ADAR1 and ADAR2. Journal of Virology 75: 8547–8555.

Taylor JM (1999a) Human hepatitis delta virus: an agent with similarities to certain satellite RNAs of plants. Current Topics in Microbiology and Immunology 239: 107–122.

Taylor JM (1999b) Replication of human hepatitis delta virus: influence of studies on subviral plant pathogens. Advances in Virus Research 54: 45–60.

Taylor JM (2005) Hepatitis delta virus. In: Mahy BWJ and ter Muelen V, (eds). Topley and Wilson's Microbiology and Microbial Infections, 10th edn. vol. 1, pp. 1269–1275. New York: Oxford University Press.

Taylor JM, Purcell RH and Farci P (2013) Hepatitis D (delta) virus. In: Knipe DM and Howley P, (eds.), Fields Virology, 6th edn, pp. 2222–2241. Philadelphia, PA: Lippincott Williams & Wilkins.

Tseng C‐H and Lai MMC (2009) Hepatitis delta virus RNA replication. Viruses 1: 818–831.

Yan H, Zhong G, Xu G, et al. (2012) Sodium taurocholate cotransporting polypeptide is a functional receptor for hepatitis B and D virus. eLife 1: 1–28.

Yurdaydin C (2012) Treatment of chronic hepatitis delta virus. Seminars in Liver Disease 32: 237–244.

Zuccola HJ, Rozzelle JE, Lemon SM, Erickson BW and Hogle JM (1998) Structural basis of the oligomerization of hepatitis delta antigen. Structure 6: 821–830.

Further Reading

Blanchet M, Sureau C and Labonte P (2014) Use of FDA approved therapeutics with hNTCP metabolic inhibitory properties to impair the HDV life cycle. Antiviral Research 106: 111–115.

Nkongolo S, Ni Y, Lempff FA, et al. (2014) Cyclosporin A inhibits hepatitis B and hepatitis D virus entry by cyclophilin‐independent interference with the NTCP receptor. Journal of Hepatology 60: 723–731.

Review of Hepatitis Delta Virus. http://en.wikipedia.org/wiki/Hepatitis_D

Taylor JM (2012) Virology of hepatitis D virus. Seminars in Liver Disease 32: 195–200.

Taylor JM (2014) RNA circles and the origin of hepatitis delta virus. World Journal of Gastroenterology 20: 2971–2978.

Watashi K, Urban S, Li W and Wakita T (2014) NTCP and beyond: opening the door to unveil hepatitis B virus entry. International Journal of Molecular Sciences 15: 2892–2905.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Taylor, John Marston(Feb 2015) Hepatitis Delta Virus. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001029.pub4]