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Fox Chase Cancer Center, PA 19111, USA.

Email the corresponding author at john.taylor@fccc.edu

Department of Biochemistry, Microbiology & Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.

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Email the corresponding author at mpelchat@uottawa.ca

Published Online:8 Mar 2010https://doi.org/10.2217/fmb.10.15

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Abstract

This article addresses some of the questions relating to how hepatitis δ virus (HDV), an agent so far unique in the animal world, might have arisen. HDV was discovered in patients infected with hepatitis B virus (HBV). It generally makes HBV infections more damaging to the liver. It is a subviral satellite agent that depends upon HBV envelope proteins for its assembly and ability to infect new cells. In other aspects of replication, HDV is both independent of and very different from HBV. In addition, the small single-stranded circular RNA genome of HDV, and its mechanism of replication, demonstrate an increasing number of similarities to the viroids – a large family of helper-independent subviral agents that cause pathogenesis in plants.

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Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

Bibliography

1 Rizzetto M, Canese MG, Arico J et al.: Immunofluorescence detection of a new antigen–antibody system associated to the hepatitis B virus in the liver and in the serum of HBsAg carriers. Gut18,997–1003 (1977).
Medline CASGoogle Scholar
2 Rizzetto M, Canese MG, Gerin JL, London WT, Sly DL, Purcell RH: Transmission of the hepatitis B virus-associated δ antigen to chimpanzees. J. Infect. Dis.141,590–602 (1980).
Medline CASGoogle Scholar
3 Taylor JM, Farci P, Purcell RH: Hepatitis δ (δ) virus. In: Fields Virology. Knipe DM (Ed.). Lippincott Williams & Wilkins, PA, USA, 3031–3046 (2007).
Google Scholar
4 Radjef N, Gordien E, Ivaniushina V et al.: Molecular phylogenetic analyses indicate a wide and ancient radiation of African hepatitis δ virus, suggesting a δ virus genus of at least seven major clades. J. Virol.78,2537–2544 (2004).
Medline CASGoogle Scholar
5 Deny P: Hepatitis δ virus genetic variability: from genotypes I, II, III to eight major clades. In: Hepatitis δ Virus. Casey JL (Ed.). Springer, Heidelberg, Germany, 151–171 (2006).▪▪ Defines the many clades of hepatitis δ virus (HDV).
Google Scholar
6 Casey JL, Niro GA, Engle RE et al.: Hepatitis B virus/hepatitis δ virus (HDV) coinfection in outbreaks of acute hepatitis in the Peruvian Amazon basin: the roles of HDV genotype III and HBV genotype F. J. Infect. Dis.174,920–926 (1996).
Medline CASGoogle Scholar
7 Seeger C, Zoulim F, Mason WS: Hepadnaviruses. In: Fields Virology. Knipe DM (Ed.). Lippincott Williams & Wilkins, PA, USA, 2977–3030 (2007).
Google Scholar
8 Taylor JM: Replication of the hepatitis δ virus RNA genome. Adv. Vir. Res.74,102–121 (2009).▪▪ Reviews how HDV RNAs are transcribed.
Google Scholar
9 Branch AD, Robertson HD: A replication cycle for viroids and small infectious RNAs. Science223,450–455 (1984).
Medline CASGoogle Scholar
10 Chen P-J, Kalpana G, Goldberg J et al.: Structure and replication of the genome of hepatitis δ virus. Proc. Natl Acad. Sci. USA83,8774–8778 (1986).
Medline CASGoogle Scholar
11 Doudna JA, Lorsch JR: Ribozyme catalysis: not different, just worse. Nat. Struct. Mol. Biol.12,395–402 (2005).
Medline CASGoogle Scholar
12 Reid CE, Lazinski DW: A host-specific function is required for ligation of a wide variety of ribozyme-processed RNAs. Proc. Natl Acad. Sci. USA97,424–429 (2000).
Medline CASGoogle Scholar
13 Gudima S, Wu S-Y, Chiang C-M, Moraleda G, Taylor J: Origin of the hepatitis δ virus mRNA. J. Virol.74,7204–7210 (2000).
Medline CASGoogle Scholar
14 Hsieh S-Y, Taylor J: Regulation of polyadenylation of HDV antigenomic RNA. J. Virol.65,6438–6446 (1991).
Medline CASGoogle Scholar
15 Chao M, Hsieh S-Y, Taylor J: Role of two forms of the hepatitis δ virus antigen: evidence for a mechanism of self-limiting genome replication. J. Virol.64,5066–5069 (1990).
Medline CASGoogle Scholar
16 Casey JL, Gerin JL: Hepatitis δ virus RNA editing: specific modification of adenosine in the antigenomic RNA. J. Virol.69,7593–7600 (1995).
Medline CASGoogle Scholar
17 Chang FL, Chen PJ, Tu SJ, Chiu MN, Wang CJ, Chen DS: The large form of hepatitis δ antigen is crucial for the assembly of hepatitis δ virus. Proc. Natl Acad. Sci. USA88,8490–8494 (1991).
Medline CASGoogle Scholar
18 Bordier BB, Ohkanda J, Liu P et al.: In vivo antiviral efficacy of prenylation inhibitors against hepatitis δ virus. J. Clin. Invest.112,407–414 (2003).
Medline CASGoogle Scholar
19 Taylor JM: Replication of human hepatitis δ virus: influence of studies on subviral plant pathogens. Adv. Virus Res.54,45–60 (1999).
Medline CASGoogle Scholar
20 Diener TO: The viroid: biological oddity or evolutionary fossil? Adv. Virus Res.57,137–184 (2001).
Medline CASGoogle Scholar
21 Owens RA, Hammond RW: Viroid pathogenicity: one process, many faces. Viruses1,298–316 (2009).
Medline CASGoogle Scholar
22 Diener TO: Potato spindle tuber “virus”. IV. A replicating, low molecular weight RNA. Virology45,411–428 (1971).
Medline CASGoogle Scholar
23 Daros J, Marcos J, Hernandez C, Flores R: Replication of avocado sunblotch viroid: Evidence for a symmetric pathway with two rolling circles and hammerhead ribozyme procesing. Proc. Natl Acad. Sci. USA91,12813–12817 (1994).
Medline CASGoogle Scholar
24 Wang K-S, Choo Q-L, Weiner AJ et al.: Structure, sequence and expression of the hepatitis δ viral genome. Nature323,508–513 (1986).
Medline CASGoogle Scholar
25 Tsagris EM, Martinez de Alba AE, Gozmanova M, Kalantidis K: Viroids. Cell Microbiol.10,2168–2179 (2008).
Medline CASGoogle Scholar
26 Tabler M, Tsagris M: Viroids: petite RNA pathogens with distinguished talents. Trends Plant Sci.9,339–348 (2004).▪▪ Reviews the many plant viroid RNAs.
Medline CASGoogle Scholar
27 Daros JA, Elena SF, Flores R: Viroids: an Ariadne’s thread into the RNA labyrinth. EMBO Rep.7,593–598 (2006).
Medline CASGoogle Scholar
28 Rocheleau L, Pelchat M: The Subviral RNA Database: a toolbox for viroids, the hepatitis δ virus and satellite RNAs research. BMC Microbiol.6,24 (2006).
MedlineGoogle Scholar
29 Flores R, Gas M-E, Molina-Serrano δ et al.: Vioroid replication: rolling-circles, enzymes and ribozymes. Viruses1,317–334 (2009).▪▪ Reviews the replication of viroids RNAs.
Medline CASGoogle Scholar
30 Flores R, Gas ME, Molina D, Hernandez C, Daros JA: Analysis of viroid replication. Methods Mol. Biol.451,167–183 (2008).
Medline CASGoogle Scholar
31 Branch AD, Robertson HD, Greer C, Gegenheimer P, Peebles C, Abelson J: Cell-free circularization of viroid progeny RNA by an RNA ligase from wheat germ. Science217,1147–1149 (1982).
Medline CASGoogle Scholar
32 Elena SF, Dopazo J, Flores R, Diener TO, Moya A: Phylogeny of viroids, viroidlike satellite RNAs, and the viroid-like domain of hepatitis δ virus RNA. Proc. Natl Acad. Sci. USA88,5631–5634 (1991).
Medline CASGoogle Scholar
33 Jenkins GM, Woelk CH, Rambaut A, Holmes EC: Testing the extent of sequence similarity among viroids, satellite RNAs, and hepatitis δ virus. J. Mol. Evol.50,98–102 (2000).
Medline CASGoogle Scholar
34 Sikora D, Greco-Stewart VS, Miron P, Pelchat M: The hepatitis δ virus RNA genome interacts with eEF1α1, p54(nrb), hnRNP-L, GAPDH and ASF/SF2. Virology390,71–78 (2009).
Medline CASGoogle Scholar
35 Dube A, Bisaillon M, Perreault JP: Identification of proteins from prunus persica that interact with peach latent mosaic viroid. J. Virol.83,12057–12067 (2009).
Medline CASGoogle Scholar
36 Schindler I-M, Muhlbach H-P: Involvement of nuclear DNA-dependent RNA polymerases in potato spindle tuber viroid replication: a reevaluation. Plant Sci.84,221–229 (1992).
CASGoogle Scholar
37 Li YJ, Macnaughton T, Gao L, Lai MM: RNA-templated replication of hepatitis δ virus: genomic and antigenomic RNAs associate with different nuclear bodies. J. Virol.80,6478–6486 (2006).
Medline CASGoogle Scholar
38 Tseng C-H, Lai MMC: Hepatitis δ virus RNA replication. Viruses1,818–831 (2009).
Medline CASGoogle Scholar
39 Tseng CH, Jeng KS, Lai MM: Transcription of subgenomic mRNA of hepatitis δ virus requires a modified hepatitis δ antigen, distinct from antigenomic RNA synthesis. J. Virol.82,9409–9416 (2008).
Medline CASGoogle Scholar
40 Greco-Stewart VS, Pelchat M: Coercion of host cellular proteins by the hepatitis δ virus. Viruses (2010) (In press).▪ Demonstrates that all three mammalian polymerases will bind to HDV RNAs.
MedlineGoogle Scholar
41 Flores R, Gas M-E, Molina-Serrano δ et al.: Viroid replication: rolling-circles, enzymes, and ribozymes. Viruses1,317–334 (2009).
Medline CASGoogle Scholar
42 Greco-Stewart VS, Miron P, Abrahem A, Pelchat M: The human RNA polymerase II interacts with the terminal stem-loop regions of the hepatitis δ virus RNA genome. Virology357,68–78 (2007).
Medline CASGoogle Scholar
43 Greco-Stewart VS, Schissel E, Pelchat M: The hepatitis δ virus RNA genome interacts with the human RNA polymerases I and III. Virology386,12–15 (2009).
Medline CASGoogle Scholar
44 Pelchat M, Perreault JP: Binding site of Escherichia coli RNA polymerase to an RNA promoter. Biochem. Biophys. Res. Commun.319,636–642 (2004).
Medline CASGoogle Scholar
45 Elena SF, Gomez G, Daros J-A: Evolutionary constraints to viroid evolution. Viruses1,241–254 (2009).
Medline CASGoogle Scholar
46 Chao M: RNA recombination in hepatitis δ virus: implications regarding the abilities of mammalian RNA polymerases. Virus Res.127,208–215 (2007).
Medline CASGoogle Scholar
47 Gudima SO, Chang J, Taylor JM: Reconstitution in cultured cells of replicating HDV RNA from pairs of less than full-length RNAs. RNA11,90–98 (2005).
Medline CASGoogle Scholar
48 Chang J, Taylor J: In vivo RNA-directed transcription, with template switching, by a mammalian RNA polymerase. EMBO J.21,157–164 (2002).▪ Demonstrates that template switching can occur during HDV RNA transcription.
Medline CASGoogle Scholar
49 Simon AE, Roossinck MJ, Havelda Z: Plant virus satellite and defective interfering RNAs: new paradigms for a new century. Ann. Rev. Phytopathol.42,415–437 (2004).
Medline CASGoogle Scholar
50 Symons RH, Randles JW: Encapsidated Circular Viroid-Like Satellite RNAs (Virusoids) of Plants. Symons RH, Randles JW (Eds). Springer-Verlag, Berlin, Germany (1999).
Google Scholar
51 Daros J, Flores R: Identification of a retroviroid-like element from plants. Proc. Natl Acad. Sci. USA92,6856–6860 (1995).
Medline CASGoogle Scholar
52 Jones FD, Ryder SP, Strobel SA: An efficient ligation reaction promoted by a Varkud satellite ribozyme with extended 5´- and 3´-termini. Nucl. Acids Res.29,5115–5120 (2001).
Medline CASGoogle Scholar
53 Kuiper MT, Sabourin JR, Lambowitz AM: Identification of the reverse transcriptase encoded by the Mauriceville and Varkud mitochondrial plasmids of Neurospora. J. Biol. Chem.265,6936–6943 (1990).
Medline CASGoogle Scholar
54 Teixeira A, Tahiri-Alaoui A, West S et al.: Autocatalytic RNA cleavage in the human δ-globin pre-mRNA promotes transcription termination. Nature432,526–530 (2004).▪ Reports a ribozyme downstream of globin mRNA.
Medline CASGoogle Scholar
55 Fong N, Ohman M, Bentley DL: Fast ribozyme cleavage releases transcripts from RNA polymerase II and aborts co-transcriptional pre-mRNA processing. Nat. Struct. Mol. Biol.16,916–922 (2009).▪ Demonstrates that ribozyme cleavage can regulate other RNA processing events.
Medline CASGoogle Scholar
56 Nie X, Chang J, Taylor JM: Alternative processing of hepatitis δ virus antigenomic RNA transcripts. J. Virol.78,4517–4524 (2004).
Medline CASGoogle Scholar
57 Brown AL, Perrotta AT, Wadkins TS, Been MD: The poly(A) site sequence in HDV RNA alters both extent and rate of self-cleavage of the antigenomic ribozyme. Nucl. Acids Res.36,2990–3000 (2008).
Medline CASGoogle Scholar
58 Salehi-Ashtiani K, Luptak A, Litovchick A, Szostak JW: A genomewide search for ribozymes reveals an HDV-like sequence in the human CPEB3 gene. Science313,1788–1792 (2006).
Medline CASGoogle Scholar
59 Webb C-HT, Riccitelli NJ, Ruminski DJ, Luptak A: Widespread occurrence of self-cleaving ribozymes. Science, 326,953 (2009).▪▪ Reports many HDV-like ribozymes.
Medline CASGoogle Scholar
60 Dinter-Gottlieb G. Designing a ribozyme from the hepatitis δ virus. In: The Unique Hepatitis δ Virus. Dinter-Gottlieb G (Ed.). RG Landes, Co. Austin, TX, USA, 33–46 (1995).
Google Scholar
61 Nigro J, Cho K, Fearon E et al.: Scrambled exons. Cell64,607–613 (1991).
Medline CASGoogle Scholar
62 Brazas R, Ganem D: A cellular homolog of hepatitis δ antigen: implications for viral replication and evolution. Science274,90–94 (1996).
Medline CASGoogle Scholar
63 Brazas R, Ganem D: δ-interacting protein A and the origin of hepatitis δ antigen. Science276,824–825 (1997).
MedlineGoogle Scholar
64 Long M, de Souza SJ, Gilbert W: δ-interacting protein A and the origin of hepatitis δ antigen. Science276,824–825 (1997).
Medline CASGoogle Scholar
65 Du X, Wang Q, Hirohashi Y, Greene MI: DIPA, which can localize to the centrosome, associates with p78/MCRS1/MSP58 and acts as a repressor of gene transcription. Exp. Mol. Pathol.81,184–190 (2006).
Medline CASGoogle Scholar
66 Yamaguchi Y, Filipovska J, Yano K et al.: Stimulation of RNA polymerase II elongation by hepatitis δ antigen. Science293,124–127 (2001).
Medline CASGoogle Scholar
67 van Hoof A, Parker R: The exosome: a proteosome for RNA? Cell12,347–350 (1999).
Google Scholar
68 Kuo MY-P, Goldberg J, Coates L, Mason W, Gerin J, Taylor J: Molecular cloning of hepatitis δ virus RNA from an infected woodchuck liver: sequence, structure, and applications. J. Virol.62,1855–1861 (1988).
Medline CASGoogle Scholar
69 Kos A, Dijkema R, Arnberg AC, van der Meide PH, Schellekens H: The hepatitis delta (δ) virus possesses a circular RNA. Nature323,558–560 (1986).
Medline CASGoogle Scholar
70 Lazinski DW, Taylor JM: Expression of hepatitis δ virus RNA deletions: cis and trans requirements for self-cleavage, ligation, and RNA packaging. J. Virol.68,2879–2888 (1994).
Medline CASGoogle Scholar
71 Wang H-W, Wu H-L, Chen D-S, Chen P-J: Identification of the functional regions required for hepatitis δ virus replication and transcription by linker-scanning mutagenesis of viral genome. Virology239,119–131 (1997).
Medline CASGoogle Scholar
72 Chang J, Gudima SO, Taylor JM: Evolution of hepatitis δ virus RNA genome following long-term replication in cell culture. J. Virol.79,13310–13316 (2005).
Medline CASGoogle Scholar
73 Ranjith-Kumar CT, Kao CC: Recombinant viral RdRps can initiate RNA synthesis from circular templates. RNA12,303–312 (2006).▪ Demonstrates that RNA polymerases can initiate transcription on circular RNAs.
Medline CASGoogle Scholar
74 Filipovska J, Konarska MM: Specific HDV RNA-templated transcription by pol II in vitro. RNA6,41–54 (2000).
Medline CASGoogle Scholar
75 Lehmann E, Brueckner F, Cramer P: Molecular basis of RNA-dependent RNA polymerase II activity. Nature450,445–449 (2007).
Medline CASGoogle Scholar
76 Katze MG, Fornek JL, Palermo RE, Walters KA, Korth MJ: Innate immune modulation by RNA viruses: emerging insights from functional genomics. Nat. Rev. Immunol.8,644–654 (2008).
Medline CASGoogle Scholar
77 Carthew RW, Sontheimer EJ: Origins and mechanisms of miRNAs and siRNAs. Cell136,642–655 (2009).
Medline CASGoogle Scholar
78 Maida Y, Yasukawa M, Furuuchi M et al.: An RNA-dependent RNA polymerase formed by TERT and the RMRP RNA. Nature461,230–235 (2009).
Medline CASGoogle Scholar
79 Zhang T, Breitbart M, Lee WH et al.: RNA viral community in human feces: prevalence of plant pathogenic viruses. PLoS Biol.4,E3 (2006).
MedlineGoogle Scholar
80 Gerritzen A, Brackmann H, van Loo B et al.: Chronic δ hepatitis in haemophiliacs. J. Med. Virol.34,188–190 (1991).
Medline CASGoogle Scholar
81 Taylor JM: Viral hepatitis d. In: Molecular Pathology of Liver Diseases. Monga P (Ed.). Springer, NY, USA (2009) (In press).
Google Scholar
101 Subviral RNA Database http://subviral.med.uottawa.ca
Google Scholar

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Acknowledgements

William Mason, Carolina Alves, Dorota Sikora and Erica Schissel, together with two anonymous reviewers, provided constructive comments on this manuscript. John Taylor acknowledges unpublished observations from Carolina Alves, Severin Gudima and Xing-Cao Nie. Martin Pelchat similarly acknowledges observations by Teodora Dimitrijevic, Dorota Sikora and Erica Schissel.

Financial & competing interests disclosure

John Taylor was supported by grants AI-256522 and CA-06927 from the NIH and by an appropriation from the Commonwealth of Pennsylvania. Martin Pelchat was supported by a grant from the Canadian Institutes of Health Research (CIHR). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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Origin of hepatitis δ virus

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Bibliography