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RNA Editing in Hepatitis Delta Virus

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Book cover Hepatitis Delta Virus

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 307))

Abstract

Hepatitis delta virus (HDV) relies heavily on host functions and on structural features of the viral RNA. A good example of this reliance is found in the process known as HDV RNA editing, which requires particular structural features in the HDV antigenome, and a host RNA editing enzyme, ADAR1. During replication, the adenosine at the amber/W site in theHDV antigenome is edited to inosine. As a result, the amber stop codon in the hepatitis delta antigen (HDAg) open reading frame is changed to a tryptophan codon and the reading frame is extended by 19 or 20 codons. Because these extra amino acids alter the functional properties of HDAg, this change serves a critical purpose in the HDV replication cycle. Analysis of the RNA secondary structures and regulation of editing in HDV genotypes I and III has indicated that although editing is essential for both genotypes, there are substantial differences. This review covers the mechanisms of RNA editing in the HDV replication cycle and the regulatory mechanisms by which HDV controls editing.

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References

  • Aruscavage PJ, Bass BL (2000) A phylogenetic analysis reveals an unusual sequence conservation within introns involved in RNA editing. RNA 6:257–269

    Article  PubMed  CAS  Google Scholar 

  • Bass BL (2002) RNA editing by adenosine deaminases that act on RNA. Annu Rev Biochem 71:817–846

    Article  PubMed  CAS  Google Scholar 

  • Bass BL, Weintraub H (1987) A developmentally regulated activity that unwinds RNA duplexes. Cell 48:607–613

    Article  PubMed  CAS  Google Scholar 

  • Bass BL, Weintraub H (1988) Anunwinding activity that covalentlymodifies its doublestranded RNA substrate. Cell 55:1089–1098

    Article  PubMed  CAS  Google Scholar 

  • Benne R, Van den Burg J, Brakenhoff JP, Sloof P, Van Boom JH, Tromp MC (1986) Major transcript of the frameshifted coxII gene fromtrypanosome mitochondria contains four nucleotides that are not encoded in the DNA. Cell 46:819–826

    Article  PubMed  CAS  Google Scholar 

  • Bergmann KF, Gerin JL (1986) Antigens of hepatitis delta virus in the liver and serum of humans and animals. J Infect Dis 154:702–706

    PubMed  CAS  Google Scholar 

  • Bonino F, Heermann KH, Rizzetto M, Gerlich WH (1986) Hepatitis delta virus: protein composition of delta antigen and its hepatitis B virus-derived envelope. J Virol 58:945–950

    PubMed  CAS  Google Scholar 

  • Bonino F, Hoyer B, Ford E, Shih JW, Purcell RH, Gerin JL (1981) The delta agent: HBsAg particles with delta antigen and RNA in the serumof an HBV carrier. Hepatology 1:127–131

    PubMed  CAS  Google Scholar 

  • Bonino F, Hoyer B, Shih JW, Rizzetto M, Purcell RH, Gerin JL (1984) Delta hepatitis agent: structural and antigenic properties of the delta-associated particle. Infect Immun 43:1000–1005

    PubMed  CAS  Google Scholar 

  • Brusa R, Zimmermann F, Koh DS, Feldmeyer D, Gass P, Seeburg PH, Sprengel R (1995) Early-onset epilepsy and postnatal lethality associated with an editing-deficient GluR-B allele in mice. Science 270:1677–1680

    PubMed  CAS  Google Scholar 

  • Casey JL (2002) RNA Editing in Hepatitis Delta Virus Genotype III Requires a Branched Double-Hairpin RNA Structure. J Virol 76:7385–7397

    Article  PubMed  CAS  Google Scholar 

  • Casey JL, Bergmann KF, Brown TL, Gerin JL (1992) Structural requirements for RNA editing in hepatitis delta virus: evidence for a uridine-to-cytidine editing mechanism. Proc Natl Acad Sci USA 89:7149–7153

    Article  PubMed  CAS  Google Scholar 

  • Casey JL, Brown TL, Colan EJ, Wignall FS, Gerin JL (1993) A genotype of hepatitis D virus that occurs in northern South America. Proc Natl Acad Sci USA 90:9016–9020

    Article  PubMed  CAS  Google Scholar 

  • Casey JL, Gerin JL (1995) Hepatitis D virus RNA editing: specific modification of adenosine in the antigenomic RNA. J Virol 69:7593–7600

    PubMed  CAS  Google Scholar 

  • Chang FL, Chen PJ, Tu SJ, Wang CJ, Chen DS (1991) The large form of hepatitis delta antigen is crucial for assembly of hepatitis delta virus. Proc Natl Acad Sci USA 88:8490–8494

    Article  PubMed  CAS  Google Scholar 

  • Chang MF, Baker SC, Soe LH, Kamahora T, Keck JG, Makino S, Govindarajan S, Lai MM (1988) Human hepatitis delta antigen is a nuclear phosphoprotein with RNA-binding activity. J Virol 62:2403–2410

    PubMed  CAS  Google Scholar 

  • Chao M, Hsieh SY, Taylor J (1990) Role of two forms of hepatitis delta virus antigen: evidence for a mechanism of self-limiting genome replication. J Virol 64:5066–5069

    PubMed  CAS  Google Scholar 

  • Cheng Q, Jayan GC, Casey JL (2003) Differential inhibition of RNA editing in hepatitis delta virus genotype III by the short and long forms of hepatitis delta antigen. J Virol 77:7786–7795

    Article  PubMed  CAS  Google Scholar 

  • Curran J, Kolakofsky D (1990) Sendai virus P gene produces multiple proteins from overlapping open reading frames. Enzyme 44:244–249

    PubMed  CAS  Google Scholar 

  • Glenn JS, Watson JA, Havel CM, White JM (1992) Identification of a prenylation site in delta virus large antigen. Science 256:1331–1333

    PubMed  CAS  Google Scholar 

  • Glenn JS, White JM (1991) trans-dominant inhibition of human hepatitis delta virus genome replication. J Virol 65:2357–2361

    PubMed  CAS  Google Scholar 

  • Gott JM, Emeson RB (2000) Functions and mechanisms of RNA editing. Annu Rev Genet 34:499–531

    Article  PubMed  CAS  Google Scholar 

  • Hartwig D, Schoeneich L, Greeve J, Schutte C, Dorn I, Kirchner H, Hennig H (2004) Interferon-alpha stimulation of liver cells enhances hepatitis delta virus RNA editing in early infection. J Hepatol 41:667–672

    Article  PubMed  CAS  Google Scholar 

  • Herb A, Higuchi M, Sprengel R, Seeburg PH (1996) Q/R site editing in kainate receptor GluR5 and GluR6 pre-mRNAs requires distant intronic sequences. ProcNatl Acad Sci USA 93:1875–1880

    Article  CAS  Google Scholar 

  • Herbert A, Rich A (2001) The role of binding domains for dsRNA and Z-DNA in the in vivo editing of minimal substrates by ADAR1. Proc Natl Acad Sci USA 98:12132–12137

    Article  PubMed  CAS  Google Scholar 

  • Higuchi M, Single FN, Kohler M, Sommer B, Sprengel R, Seeburg PH (1993) RNA editing of AMPA receptor subunit GluR-B: a base-paired intron-exon structure determines position and efficiency. Cell 75:1361–1370

    Article  PubMed  CAS  Google Scholar 

  • Hsu SC, Syu WJ, Sheen IJ, Liu HT, Jeng KS, Wu JC (2002) Varied assembly and RNA editing efficiencies between genotypes I and II hepatitis D virus and their implications. Hepatology 35:665–672

    Article  PubMed  CAS  Google Scholar 

  • Hwang SB, Lee CZ, Lai MM (1992) Hepatitis delta antigen expressed by recombinant baculoviruses: comparison of biochemical properties and post-translational modifications between the large and small forms. Virology 190:413–422

    Article  PubMed  CAS  Google Scholar 

  • Ilan Y, Klein A, Taylor J, Tur-Kaspa R (1992) Resistance of hepatitis delta virus replication to interferon-alpha treatment in transfected human cells. J Infect Dis 166:1164–1166

    PubMed  CAS  Google Scholar 

  • Ivaniushina V, Radjef N, Alexeeva M, Gault E, Semenov S, Salhi M, Kiselev O, Deny P (2001) Hepatitis delta virus genotypes I and II cocirculate in an endemic area of Yakutia, Russia. J Gen Virol 82:2709–2718

    PubMed  CAS  Google Scholar 

  • Jayan GC, Casey JL (2002a) Increased RNA editing and inhibition of hepatitis delta virus replication by high-level expression of ADAR1 and ADAR2. J Virol 76:3819–3827

    Article  PubMed  CAS  Google Scholar 

  • Jayan GC, Casey JL (2002b) Inhibition of hepatitis delta virus RNA editing by short inhibitory RNA-mediated knockdown of Adar1 but not Adar2 expression. J Virol 76:12399–12404

    Article  PubMed  CAS  Google Scholar 

  • Jayan GC, Casey JL (2005) Effects of conserved RNA secondary structures on hepatitis delta virus genotype I RNA editing, replication, and virus production. J Virol 79:11187–11193

    Article  PubMed  CAS  Google Scholar 

  • Kuo MY, Chao M, Taylor J (1989) Initiation of replication of the human hepatitis delta virus genome from cloned DNA: role of delta antigen. J Virol 63:1945–1950

    PubMed  CAS  Google Scholar 

  • Lehmann KA, Bass BL (1999) The importance of internal loops within RNA substrates of ADAR1. J Mol Biol 291:1–13

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Herbert A, Rich A, Samuel CE (1998) Double-stranded RNA-specific adenosine deaminase: nucleic acid binding properties. Methods 15:199–205

    Article  PubMed  Google Scholar 

  • Liu Y, Samuel CE (1996) Mechanism of interferon action: functionally distinct RNAbinding and catalytic domains in the interferon-inducible, double-stranded RNAspecific adenosine deaminase. J Virol 70:1961–1968

    PubMed  CAS  Google Scholar 

  • Lomeli H, Mosbacher J, Melcher T, Hoger T, Geiger JR, Kuner T, Monyer H, Higuchi M, Bach A, Seeburg PH (1994) Control of kinetic properties of AMPA receptor channels by nuclear RNA editing. Science 266:1709–1713

    PubMed  CAS  Google Scholar 

  • Luo GX, Chao M, Hsieh SY, Sureau C, Nishikura K, Taylor J (1990) A specific base transition occurs on replicating hepatitis delta virus RNA. J Virol 64:1021–1027

    PubMed  CAS  Google Scholar 

  • Macnaughton TB, Lai MM (2002) Large hepatitis delta antigen is not a suppressor of hepatitis delta virus RNA synthesis once RNA replication is established. J Virol 76:9910–9919

    Article  PubMed  CAS  Google Scholar 

  • Makino S, Chang MF, Shieh CK, Kamahora T, Vannier DM, Govindarajan S, Lai MM (1987) Molecular cloning and sequencing of a human hepatitis delta virus RNA. Nature 329:343–346

    Article  PubMed  CAS  Google Scholar 

  • McNair AN, Cheng D, Monjardino J, Thomas HC, Kerr IM (1994) Hepatitis delta virus replication in vitro is not affected by interferon-alpha or-gamma despite intact cellular responses to interferon and dsRNA. J Gen Virol 75:1371–1378

    PubMed  CAS  Google Scholar 

  • Melcher T, Maas S, Herb A, Sprengel R, Seeburg PH, Higuchi M (1996) A mammalian RNA editing enzyme. Nature 379:460–464

    Article  PubMed  CAS  Google Scholar 

  • Modahl LE, Lai MM (2000) The large delta antigen of hepatitis delta virus potently inhibits genomic but not antigenomic RNA synthesis: a mechanism enabling initiation of viral replication. J Virol 74:7375–7380

    Article  PubMed  CAS  Google Scholar 

  • Niro GA, Smedile A, Andriulli A, Rizzetto M, Gerin JL, Casey JL (1997) The predominance of hepatitis delta virus genotype I among chronically infected Italian patients. Hepatology 25:728–734

    Article  PubMed  CAS  Google Scholar 

  • O’Connell MA, Krause S, Higuchi M, Hsuan JJ, Totty NF, Jenny A, Keller W (1995) Cloning of cDNAs encoding mammalian double-stranded RNA-specific adenosine deaminase. Mol Cell Biol 15:1389–1397

    PubMed  CAS  Google Scholar 

  • Ohman M, Kallman AM, Bass BL (2000) In vitro analysis of the binding of ADAR2 to the pre-mRNA encoding the GluR-B R/G site. RNA 6:687–697

    Article  PubMed  CAS  Google Scholar 

  • Patterson JB, Samuel CE (1995) Expression and regulation by interferon of a doublestranded-RNA-specific adenosine deaminase fromhuman cells: evidence for two forms of the deaminase. Mol Cell Biol 15:5376–5388

    PubMed  CAS  Google Scholar 

  • Paul MS, Bass BL (1998) Inosine exists in mRNA at tissue-specific levels and is most abundant in brain mRNA. EMBO J 17:1120–1127

    Article  PubMed  CAS  Google Scholar 

  • Polson AG, Bass BL (1994) Preferential selection of adenosines for modification by double-stranded RNA adenosine deaminase. EMBO J 13:5701–5711

    PubMed  CAS  Google Scholar 

  • Polson AG, Bass BL, Casey JL (1996) RNA editing of hepatitis delta virus antigenome by dsRNA-adenosine deaminase. Nature 380:454–456

    Article  PubMed  CAS  Google Scholar 

  • Polson AG, Ley HL, 3rd, Bass BL, Casey JL (1998) Hepatitis delta virus RNA editing is highly specific for the amber/Wsite and is suppressed by hepatitis delta antigen. Mol Cell Biol 18:1919–1926

    PubMed  CAS  Google Scholar 

  • Radjef N, Gordien E, Ivaniushina V, Gault E, Anais P, Drugan T, Trinchet JC, Roulot D, Tamby M, Milinkovitch MC and others (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 78:2537–2544

    Article  PubMed  CAS  Google Scholar 

  • Ryu WS, Bayer M, Taylor J (1992) Assembly of hepatitis delta virus particles. J Virol 66:2310–2315

    PubMed  CAS  Google Scholar 

  • Sato S, Cornillez-Ty C, Lazinski DW (2004) By inhibiting replication, the large hepatitis delta antigen can indirectly regulate amber/W editing and its own expression. J Virol 78:8120–8134

    Article  PubMed  CAS  Google Scholar 

  • Sato S, Wong SK, Lazinski DW (2001) Hepatitis delta virus minimal substrates competent for editing by adar1 and adar2. J Virol 75:8547–8555

    Article  PubMed  CAS  Google Scholar 

  • Scott J (1989) Messenger RNA editing and modification. Curr Opin Cell Biol 1:1141–1147

    PubMed  CAS  Google Scholar 

  • Seeburg PH (2002) A-to-I editing: new and old sites, functions and speculations. Neuron 35:17–20

    Article  PubMed  CAS  Google Scholar 

  • Seeburg PH, Higuchi M, Sprengel R (1998) RNA editing of brain glutamate receptor channels: mechanism and physiology. Brain Res Brain Res Rev 26:217–229.

    Article  PubMed  CAS  Google Scholar 

  • Shakil AO, Hadziyannis S, Hoofnagle JH, Di Bisceglie AM, Gerin JL, Casey JL (1997) Geographic distribution and genetic variability of hepatitis delta virus genotype I. Virology 234:160–167

    Article  PubMed  CAS  Google Scholar 

  • Sureau C, Taylor J, Chao M, Eichberg JW, Lanford RE (1989) Cloned hepatitis delta virus cDNA is infectious in the chimpanzee. J Virol 63:4292–4297

    PubMed  CAS  Google Scholar 

  • Wagner RW, Smith JE, Cooperman BS, Nishikura K (1989) A double-stranded RNA unwinding activity introduces structural alterations by means of adenosine to inosine conversions in mammalian cells and Xenopus eggs. Proc Natl Acad Sci USA 86:2647–2651

    Article  PubMed  CAS  Google Scholar 

  • Wang JG, Cullen J, Lemon SM(1992) Immunoblot analysis demonstrates that the large and small forms of hepatitis delta virus antigen have different C-terminal amino acid sequences. J Gen Virol 73:183–188

    Article  PubMed  CAS  Google Scholar 

  • Wang KS, Choo QL, Weiner AJ, Ou JH, Najarian RC, Thayer RM, Mullenbach GT, Denniston KJ, Gerin JL, Houghton M (1986) Structure, sequence and expression of the hepatitis delta viral genome. Nature 323:508–514

    Article  PubMed  CAS  Google Scholar 

  • Wang Q, Khillan J, Gadue P, Nishikura K (2000) Requirement of the RNA editing deaminase ADAR1 gene for embryonic erythropoiesis. Science 290:1765–1768

    Article  PubMed  CAS  Google Scholar 

  • Weiner AJ, Choo QL, Wang KS, Govindarajan S, Redeker AG, Gerin JL, Houghton M (1988) A single antigenomic open reading frame of the hepatitis delta virus encodes the epitope(s) of both hepatitis delta antigen polypeptides p24 delta and p27 delta. J Virol 62:594–599

    PubMed  CAS  Google Scholar 

  • Wong SK, Lazinski DW (2002) Replicating hepatitis delta virus RNA is edited in the nucleus by the small form of ADAR1. Proc Natl Acad Sci USA 99:15118–15123

    Article  PubMed  CAS  Google Scholar 

  • Wong SK, Sato S, Lazinski DW (2001) Substrate recognition by ADAR1 and ADAR2. RNA 7:846–858

    Article  PubMed  CAS  Google Scholar 

  • Wu TT, Bichko VV, Ryu WS, Lemon SM, Taylor JM (1995) Hepatitis delta virusmutant: effect on RNA editing. J Virol 69:7226–7231

    PubMed  CAS  Google Scholar 

  • Xia YP, Chang MF, Wei D, Govindarajan S, Lai MM (1990) Heterogeneity of hepatitis delta antigen. Virology 178:331–336

    Article  PubMed  CAS  Google Scholar 

  • Yang A, Papaioannou C, Hadzyannis S, Thomas H, Monjardino J (1995) Base changes at positions 1014 and 578 of delta virus RNA in Greek isolates maintain base pair in rod conformation with efficient RNA editing. J Med Virol 47:113–119

    PubMed  CAS  Google Scholar 

  • Yang JH, Sklar P, Axel R, Maniatis T (1997) Purification and characterization of a human RNA adenosine deaminase for glutamate receptor B pre-mRNA editing. ProcNatl Acad Sci USA 94:4354–4359

    Article  CAS  Google Scholar 

  • Zheng H, Fu TB, Lazinski D, Taylor J (1992) Editing on the genomic RNA of human hepatitis delta virus. J Virol 66:4693–4697

    PubMed  CAS  Google Scholar 

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© 2006 Springer-Verlag Berlin Heidelberg

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Casey, J.L. (2006). RNA Editing in Hepatitis Delta Virus. In: Casey, J.L. (eds) Hepatitis Delta Virus. Current Topics in Microbiology and Immunology, vol 307. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-29802-9_4

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