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The Woodchuck Model of HDV Infection

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

Abstract

The Eastern woodchuck, Marmota monax, has been a useful model system for the study of the natural history of hepadnavirus infection and for the development and preclinical testing of antiviral therapies. The model has also been used for hepatitis delta virus (HDV). In this chapter several new applications of the woodchuck model of HDV infection are presented and discussed. The development of a woodchuck HDV inoculum derived from a molecular clone has facilitated the analysis of viral genetic changes occurring during acute and chronic infection. This analysis has provided insights into one of the more important aspects of the natural history of HDV infection—whether a superinfection becomes chronic. These results could renew interest in further vaccine development. An effective therapy for chronic HDV infection remains an important clinical goal for this agent, particularly because of the severity of the disease and the inability of current hepadnaviral therapies to ameliorate it. The recent application of the woodchuck model of chronic HDV infection to therapeutic development has yielded promising results which indicate that targeting the hepadnavirus surface protein may be a successful therapeutic strategy for HDV.

Keywords

Hepatitis Delta Virus HBsAg Level Woolly Monkey Woodchuck Hepatitis Virus Hepatitis Delta Virus Infection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Bergmann KF, Casey JL, Tennant BC, Gerin JL (1993) Modulation of hepatitis delta virus infection by vaccination with synthetic peptides: a preliminary study in the woodchuck model. Prog Clin Biol Res 382:181–187PubMedGoogle Scholar
  2. Bergmann KF, Cote PJ, Moriarty A, Gerin JL (1989) Hepatitis delta antigen. Antigenic structure and humoral immune response [published erratum appears in J Immunol 1990 Feb 1;144(3):1151]. J Immunol 143:3714–3721PubMedGoogle Scholar
  3. Casey JL, Cote PJ, Toshkov IA, Chu CK, Gerin JL, Hornbuckle WE, Tennant BC, Korba BE (2005) Clevudine inhibits hepatitis delta virus viremia: a pilot study in chronically infected woodchucks. Antimicrob Agents Chemother 49: 4396–4399PubMedCrossRefGoogle Scholar
  4. Chao YC, Tang HS, Hsu CT (1994) Evolution rate of hepatitis delta virus RNA isolated in Taiwan. J Med Virol 43:397–403PubMedGoogle Scholar
  5. Choi SS, Rasshofer R, Roggendorf M (1988) Propagation of woodchuck hepatitis delta virus in primary woodchuck hepatocytes. Virology 167:451–457PubMedGoogle Scholar
  6. D’Ugo E, Paroli M, Palmieri G, Giuseppetti R, Argentini C, Tritarelli E, Bruni R, Barnaba V, Houghton M, Rapicetta M (2004) Immunization of woodchucks with adjuvanted sHDAg (p24): immune response and outcome following challenge. Vaccine 22:457–466PubMedCrossRefGoogle Scholar
  7. Dienstag JL, Perrillo RP, Schiff ER, Bartholomew M, Vicary C, Rubin M (1995) A preliminary trial of lamivudine for chronic hepatitis B infection. N Engl J Med 333:1657–1661PubMedCrossRefGoogle Scholar
  8. Farci P, Shimoda A, Coiana A, Diaz G, Peddis G, Melpolder JC, Strazzera A, Chien DY, Munoz SJ, Balestrieri A and others (2000) The outcome of acute hepatitis C predicted by the evolution of the viral quasispecies. Science 288:339–344PubMedCrossRefGoogle Scholar
  9. Fattovich G, Giustina G, Christensen E, Pantalena M, Zagni I, Realdi G, Schalm SW (2000) Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B. The European Concerted Action on Viral Hepatitis (Eurohep). Gut 46:420–426PubMedCrossRefGoogle Scholar
  10. Feld J, Locarnini S (2002) Antiviral therapy for hepatitis B virus infections: new targets and technical challenges. J. Clin. Virol. 25:267–283PubMedCrossRefGoogle Scholar
  11. Fiedler M, Lu M, Siegel F, Whipple J, Roggendorf M (2001) Immunization of woodchucks (Marmota monax) with hepatitis delta virus DNA vaccine. Vaccine 19:4618–4626PubMedCrossRefGoogle Scholar
  12. Gerin JL, Casey JL, Purcell RH (2001) Hepatitis Delta Virus. In: Knipe DM, Howley PM, (eds) Field’s Virology. 4 ed. Lippincott, Williams & Wilkins, Philadelphia, PA, pp 3037–3050Google Scholar
  13. Imazeki F, Omata M, Ohto M (1990) Heterogeneity and evolution rates of delta virus RNA sequences. J Virol 64:5594–5599PubMedGoogle Scholar
  14. Karayiannis P, Saldanha J, Jackson AM, Luther S, Goldin R, Monjardino J, Thomas HC (1993) Partial control of hepatitis delta virus superinfection by immunisation of woodchucks (Marmota monax) with hepatitis delta antigen expressed by a recombinant vaccinia or baculovirus. J Med Virol 41:210–214PubMedGoogle Scholar
  15. Karayiannis P, Saldanha J, Monjardino J, Goldin R, Main J, Luther S, Easton M, Ponzetto A, Thomas HC (1990) Immunization of woodchucks with recombinant hepatitis delta antigen does not protect against hepatitis delta virus infection. Hepatology 12:1125–1128PubMedGoogle Scholar
  16. Korba BE, Cote PJ, Menne S, Toshkov IA, Baldwin BH, Wells FV, Tennant BC, Gerin JL (2004) Clevudine therapy with vaccine inhibits progression of chronic hepatitis and delays onset of hepatocellular carcinoma in chronic woodchuck hepatitis virus infection. Antiviral Therapy 9:937–952PubMedGoogle Scholar
  17. Lai CL, Chien RN, Leung NW, Chang TT, Guan R, Tai DI, Ng KY, Wu PC, Dent JC, Barber J and others (1998) A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group. N Engl J Med 339:61–68PubMedCrossRefGoogle Scholar
  18. Lanford RE, Chavez D, Brasky KM, Burns RB, 3rd, Rico-Hesse R (1998) Isolation of a hepadnavirus from the woolly monkey, a New World primate. Proc Natl Acad Sci U S A 95:5757–5761PubMedCrossRefGoogle Scholar
  19. Lau DT, Doo E, Park Y, Kleiner DE, Schmid P, Kuhns MC, Hoofnagle JH (1999) Lamivudine for chronic delta hepatitis. Hepatology 30:546–549PubMedCrossRefGoogle Scholar
  20. Lee CM, Bih FY, Chao YC, Govindarajan S, Lai MM (1992) Evolution of hepatitis delta virus RNA during chronic infection. Virology 188:265–273PubMedCrossRefGoogle Scholar
  21. Marcellin P, Mommeja-Marin H, Sacks SL, Lau GK, Sereni D, Bronowicki JP, Conway B, Trepo C, Blum MR, Yoo BC and others (2004) A phase II dose-escalating trial of clevudine in patients with chronic hepatitis B. Hepatology 40:140–148PubMedCrossRefGoogle Scholar
  22. Menne S, Roneker CA, Korba BE, Gerin JL, Tennant BC, Cote PJ (2002) Immunization with surface antigen vaccine alone and after treatment with 1-(2-fluoro-5-methyl-βL-arabinofuranosyl)-uracil (L-FMAU) breaks humoral and cell-mediated immune tolerance in chronic woodchuck hepatitis virus infection. J Virol 76:5305–5314PubMedCrossRefGoogle Scholar
  23. Negro F, Korba BE, Forzani B, Baroudy BM, Brown TL, Gerin JL, Ponzetto A (1989) Hepatitis delta virus (HDV) and woodchuck hepatitis virus (WHV) nucleic acids in tissues of HDV-infected chronic WHV carrier woodchucks. J Virol 63:1612–1618PubMedGoogle Scholar
  24. Netter HJ, Kajino K, Taylor JM (1993) Experimental transmission of human hepatitis delta virus to the laboratory mouse. J Virol 67:3357–3362PubMedGoogle Scholar
  25. Netter HJ, Wu TT, Bockol M, Cywinski A, Ryu WS, Tennant BC, Taylor JM (1995) Nucleotide sequence stability of the genome of hepatitis delta virus. J Virol 69:1687–1692PubMedGoogle Scholar
  26. Nevens F, Main J, Honkoop P, Tyrrell DL, Barber J, Sullivan MT, Fevery J, De Man RA, Thomas HC (1997) Lamivudine therapy for chronic hepatitis B: a six-month randomized dose-ranging study. Gastroenterology 113:1258–1263PubMedCrossRefGoogle Scholar
  27. Niro GA, Rosina F, Rizzetto M (2005) Treatment of hepatitis D. J Viral Hepat 12:2–9PubMedCrossRefGoogle Scholar
  28. Peek SF, Cote PJ, Jacob JR, Toshkov IA, Hornbuckle WE, Baldwin BH, Wells FV, Chu CK, Gerin JL, Tennant BC and others (2001) Antiviral activity of L-FMAU (1-(2-fluoro-5-methyl-b_L-arabinofuranosyl) uracil) against WHV replication and gene expression in chronically infected woodchucks. Hepatology 33:254–266PubMedCrossRefGoogle Scholar
  29. Ponzetto A, Cote PJ, Popper H, Hoyer BH, London WT, Ford EC, Bonino F, Purcell RH, Gerin JL (1984) Transmission of the hepatitis B virus-associated delta agent to the eastern woodchuck. Proc Natl Acad Sci U S A 81:2208–2212PubMedCrossRefGoogle Scholar
  30. Ponzetto A, Forzani B, Smedile A, Hele C, Avanzini L, Novara R, Canese MG (1987) Acute and chronic delta infection in the woodchuck. Prog Clin Biol Res 234:37–46PubMedGoogle Scholar
  31. Purcell RH, Satterfield WC, Bergmann KF, Smedile A, Ponzetto A, Gerin JL (1987) Experimental hepatitis delta virus infection in the chimpanzee. In: Rizzetto M, Gerin JL, Purcell RH, (eds) The hepatitis delta virus and its infection. Alan R. Liss, New York, pp 27–36Google Scholar
  32. Rizzetto M, Hoyer B, Canese MG, Shih JW, Purcell RH, Gerin JL (1980) delta Agent: association of delta antigen with hepatitis B surface antigen and RNA in serum of delta-infected chimpanzees. Proc Natl Acad Sci U S A 77:6124–6128PubMedCrossRefGoogle Scholar
  33. Rizzetto M, Verme G, Recchia S, Bonino F, Farci P, Arico S, Calzia R, Picciotto A, Colombo M, Popper H (1983) Chronic hepatitis in carriers of hepatitis B surface antigen, with intrahepatic expression of the delta antigen. An active and progressive disease unresponsive to immunosuppressive treatment. Ann Intern Med 98:437–441PubMedGoogle Scholar
  34. Ryu WS, Bayer M, Taylor J (1992) Assembly of hepatitis delta virus particles. J Virol 66:2310–2315PubMedGoogle Scholar
  35. Schlipkoter U, Ponzetto A, Fuchs K, Rasshofer R, Choi SS, Roos S, Rapicetta M, Roggendorf M (1990) Different outcomes of chronic hepatitis delta virus infection in woodchucks. Liver 10:291–301PubMedGoogle Scholar
  36. Smedile A, Casey JL, Cote PJ, Durazzo M, Lavezzo B, Purcell RH, Rizzetto M, Gerin JL (1998) Hepatitis D viremia following orthotopic liver transplantation involves a typical HDV virion with a hepatitis B surface antigen envelope. Hepatology 27:1723–1729PubMedCrossRefGoogle Scholar
  37. Smedile A, Rizzetto M, Gerin JL (1994) Advances in hepatitis D virus biology and disease. Prog Liver Dis 12:157–175PubMedGoogle Scholar
  38. Taylor J, Mason W, Summers J, Goldberg J, Aldrich C, Coates L, Gerin J, Gowans E (1987) Replication of human hepatitis delta virus in primary cultures of woodchuck hepatocytes. J Virol 61:2891–2895PubMedGoogle Scholar
  39. Tennant BC, Gerin JL (1994) The woodchuck model of hepatitis B virus infection. In: Shafritz DA, (ed) The Liver: Biology and Pathology. 3rd ed. Raven Press, Ltd., New York, pp 1455–1466Google Scholar
  40. Wang JG, Jansen RW, Brown EA, Lemon SM (1990) Immunogenic domains of hepatitis delta virus antigen: peptide mapping of epitopes recognized by human and woodchuck antibodies. J Virol 64:1108–1116PubMedGoogle Scholar
  41. Wolters LM, van Nunen AB, Honkoop P, Vossen AC, Niesters HG, Zondervan PD, de Man RA (2000) Lamivudine-high dose interferon combination therapy for chronic hepatitis B patients co-infected with the hepatitis D virus. J Viral Hepatitis 7:428–434CrossRefGoogle Scholar
  42. Wright TL, Pereira B (1995) Liver transplantation for chronic viral hepatitis. Liver Transplant Surg 1:30–42CrossRefGoogle Scholar
  43. Yurdaydin C, Bozkaya H, Gurel S, Tillmann HL, Aslan N, Okcu-Heper A, Erden E, Yalcin K, Iliman N, Uzunalimoglu O and others (2002) Famciclovir treatment of chronic delta hepatitis. J Hepatol 37:266–271PubMedCrossRefGoogle Scholar
  44. Zhu Y, Yamamoto T, Cullen J, Saputelli J, Aldrich CE, Miller DS, Litwin S, Furman PA, Jilbert AR, Mason WS (2001) Kinetics of hepadnavirus loss from the liver during inhibition of viral DNA synthesis. J Virol 75:311–322PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  1. 1.Department of Microbiology and ImmunologyGeorgetown University Medical CenterWashington, DCUSA
  2. 2.Department of Microbiology and Immunology and Division of Molecular Virology and ImmunologyGeorgetown University Medical CenterWashington, DCUSA

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