Journal of Hepatology
Volume 49, Issue 6 , Pages 908-915 , December 2008

Chimeric GB virus B genomes containing hepatitis C virus p7 are infectious in vivo

  • Stephen Griffin

      Affiliations

    • Institute of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
    • Corresponding Author InformationCorresponding author. Tel.: +44 113 3433154; fax: +44 113 3435638.
    • ,
  • Rachel Trowbridge

      Affiliations

    • Institute of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
    • ,
  • Pia Thommes

      Affiliations

    • Department of Virology, GSK Medicines Research Centre, Stevenage, UK
    • ,
  • Nigel Parry

      Affiliations

    • Department of Virology, GSK Medicines Research Centre, Stevenage, UK
    • ,
  • David Rowlands

      Affiliations

    • Institute of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
    • ,
  • Mark Harris

      Affiliations

    • Institute of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
    • ,
  • Helen Bright

      Affiliations

    • Department of Virology, GSK Medicines Research Centre, Stevenage, UK
    • Present address: Pfizer Ltd., Sandwich, Kent, United Kingdom.

Received 17 March 2008 ,Revised 20 June 2008 ,Accepted 7 July 2008.

References 

  1. Pawlotsky JM. Therapy of hepatitis C: from empiricism to eradication. Hepatology. 2006;43:S207–S220
  2. Pawlotsky JM. Hepatitis C virus genetic variability: pathogenic and clinical implications. Clin Liver Dis. 2003;7:45–66
  3. Mercer DF, Schiller DE, Elliott JF, Douglas DN, Hao C, Rinfret A, et al. Hepatitis C virus replication in mice with chimeric human livers. Nat Med. 2001;7:927–933
  4. Galun E, Burakova T, Ketzinel M, Lubin I, Shezen E, Kahana Y, et al. Hepatitis C virus viremia in SCID–>BNX mouse chimera. J Infect Dis. 1995;172:25–30
  5. Ohba K, Mizokami M, Lau JY, Orito E, Ikeo K, Gojobori T. Evolutionary relationship of hepatitis C, pesti-, flavi-, plantviruses, and newly discovered GB hepatitis agents. FEBS Lett. 1996;378:232–234
  6. Muerhoff AS, Leary TP, Simons JN, Pilot-Matias TJ, Dawson GJ, Erker JC, et al. Genomic organization of GB viruses A and B: two new members of the Flaviviridae associated with GB agent hepatitis. J Virol. 1995;69:5621–5630
  7. Jacob JR, Lin KC, Tennant BC, Mansfield KG. GB virus B infection of the common marmoset (Callithrix jacchus) and associated liver pathology. J Gen Virol. 2004;85:2525–2533
  8. Lanford RE, Chavez D, Notvall L, Brasky KM. Comparison of tamarins and marmosets as hosts for GBV-B infections and the effect of immunosuppression on duration of viremia. Virology. 2003;311:72–80
  9. Bukh J, Apgar CL, Govindarajan S, Purcell RH. Host range studies of GB virus-B hepatitis agent, the closest relative of hepatitis C virus, in New World monkeys and chimpanzees. J Med Virol. 2001;65:694–697
  10. Beames B, Chavez D, Guerra B, Notvall L, Brasky KM, Lanford RE. Development of a primary tamarin hepatocyte culture system for GB virus-B: a surrogate model for hepatitis C virus. J Virol. 2000;74:11764–11772
  11. Bright H, Carroll AR, Watts PA, Fenton RJ. Development of a GB virus B marmoset model and its validation with a novel series of hepatitis C virus NS3 protease inhibitors. J Virol. 2004;78:2062–2071
  12. Beames B, Chavez D, Lanford RE. GB virus B as a model for hepatitis C virus. Ilar J. 2001;42:152–160
  13. Pletnev AG, Bray M, Huggins J, Lai CJ. Construction and characterization of chimeric tick-borne encephalitis/dengue type 4 viruses. Proc Natl Acad Sci USA. 1992;89:10532–10536
  14. Chambers TJ, Nestorowicz A, Mason PW, Rice CM. Yellow fever/Japanese encephalitis chimeric viruses: construction and biological properties. J Virol. 1999;73:3095–3101
  15. Rijnbrand R, Yang Y, Beales L, Bodola F, Goettge K, Cohen L, et al. A chimeric GB virus B with 5′ nontranslated RNA sequence from hepatitis C virus causes hepatitis in tamarins. Hepatology. 2005;41:986–994
  16. Clarke D, Griffin S, Beales L, Gelais CS, Burgess S, Harris M, et al. Evidence for the formation of a heptameric ion channel complex by the hepatitis C virus p7 protein in vitro. J Biol Chem. 2006;281:37057–37068
  17. Griffin SD, Harvey R, Clarke DS, Barclay WS, Harris M, Rowlands DJ. A conserved basic loop in hepatitis C virus p7 protein is required for amantadine-sensitive ion channel activity in mammalian cells but is dispensable for localization to mitochondria. J Gen Virol. 2004;85:451–461
  18. Griffin SD, Beales LP, Clarke DS, Worsfold O, Evans SD, Jaeger J, et al. The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine. FEBS Lett. 2003;535:34–38
  19. Premkumar A, Wilson L, Ewart GD, Gage PW. Cation-selective ion channels formed by p7 of hepatitis C virus are blocked by hexamethylene amiloride. FEBS Lett. 2004;557:99–103
  20. Pavlovic D, Neville DC, Argaud O, Blumberg B, Dwek RA, Fischer WB, et al. The hepatitis C virus p7 protein forms an ion channel that is inhibited by long-alkyl-chain iminosugar derivatives. Proc Natl Acad Sci USA. 2003;100:6104–6108
  21. Sakai A, Claire MS, Faulk K, Govindarajan S, Emerson SU, Purcell RH, et al. The p7 polypeptide of hepatitis C virus is critical for infectivity and contains functionally important genotype-specific sequences. Proc Natl Acad Sci USA. 2003;100:11646–11651
  22. Carrere-Kremer S, Montpellier-Pala C, Cocquerel L, Wychowski C, Penin F, Dubuisson J. Subcellular localization and topology of the p7 polypeptide of hepatitis C virus. J Virol. 2002;76:3720–3730
  23. Griffin S, Clarke D, McCormick C, Rowlands D, Harris M. Signal peptide cleavage and internal targeting signals direct the hepatitis C virus p7 protein to distinct intracellular membranes. J Virol. 2005;79:15525–15536
  24. Haqshenas G, Mackenzie JM, Dong X, Gowans EJ. Hepatitis C virus p7 protein is localized in the endoplasmic reticulum when it is encoded by a replication-competent genome. J Gen Virol. 2007;88:134–142
  25. Jones CT, Murray CL, Eastman DK, Tassello J, Rice CM. Hepatitis C virus p7 and NS2 proteins are essential for production of infectious virus. J Virol. 2007;81:8374–8383
  26. Steinmann E, Penin F, Kallis S, Patel AH, Bartenschlager R, Pietschmann T. Hepatitis C Virus p7 protein is crucial for assembly and release of infectious virions. PLoS Pathog. 2007;3:e103
  27. Ghibaudo D, Cohen L, Penin F, Martin A. Characterization of GB virus B polyprotein processing reveals the existence of a novel 13-kDa protein with partial homology to hepatitis C virus p7 protein. J Biol Chem. 2004;279:24965–24975
  28. Takikawa S, Engle RE, Emerson SU, Purcell RH, St Claire M, Bukh J. Functional analyses of GB virus B p13 protein: development of a recombinant GB virus B hepatitis virus with a p7 protein. Proc Natl Acad Sci USA. 2006;103:3345–3350
  29. Premkumar A, Dong X, Haqshenas G, Gage PW, Gowans EJ. Amantadine inhibits the function of an ion channel encoded by GB virus B, but fails to inhibit virus replication. Antiviral Ther. 2006;11:289–295
  30. Bukh J, Apgar CL, Yanagi M. Toward a surrogate model for hepatitis C virus: an infectious molecular clone of the GB virus-B hepatitis agent. Virology. 1999;262:470–478
  31. Yanagi M, St Claire M, Shapiro M, Emerson SU, Purcell RH, Bukh J. Transcripts of a chimeric cDNA clone of hepatitis C virus genotype 1b are infectious in vivo. Virology. 1998;244:161–172
  32. Hope RG, Murphy DJ, McLauchlan J. The domains required to direct core proteins of hepatitis C virus and GB virus-B to lipid droplets share common features with plant oleosin proteins. J Biol Chem. 2002;277:4261–4270
  33. Targett-Adams P, Schaller T, Hope G, Lanford RE, Lemon SM, Martin A, et al. Signal peptide peptidase cleavage of GB virus B core protein is required for productive infection in vivo. J Biol Chem. 2006;281:29221–29227
  34. Isherwood BJ, Patel AH. Analysis of the processing and transmembrane topology of the E2p7 protein of hepatitis C virus. J Gen Virol. 2005;86:667–676
  35. Carrere-Kremer S, Montpellier C, Lorenzo L, Brulin B, Cocquerel L, Belouzard S, et al. Regulation of hepatitis C virus polyprotein processing by signal peptidase involves structural determinants at the p7 sequence junctions. J Biol Chem. 2004;279:41384–41392
  36. Mizushima H, Hijikata M, Asabe S, Hirota M, Kimura K, Shimotohno K. Two hepatitis C virus glycoprotein E2 products with different C termini. J Virol. 1994;68:6215–6222
  37. Lin C, Lindenbach BD, Pragai BM, McCourt DW, Rice CM. Processing in the hepatitis C virus E2-NS2 region: identification of p7 and two distinct E2-specific products with different C termini. J Virol. 1994;68:5063–5073
  38. Haqshenas G, Dong X, Netter H, Torresi J, Gowans EJ. A chimeric GB virus B encoding the hepatitis C virus hypervariable region 1 is infectious in vivo. J Gen Virol. 2007;88:895–902
  39. St. Gelais C, Tuthill TJ, Clarke DS, Rowlands DJ, Harris M, Griffin S. Inhibition of hepatitis C virus p7 membrane channels in a liposome-based assay system. Antiviral Res. 2007;76:48–58
  40. Lindenbach BD, Evans MJ, Syder AJ, Wolk B, Tellinghuisen TL, Liu CC, et al. Complete replication of hepatitis C virus in cell culture. Science. 2005;309:623–626
  41. Wakita T, Pietschmann T, Kato T, Date T, Miyamoto M, Zhao Z, et al. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med. 2005;11:791–796
  42. Zhong J, Gastaminza P, Cheng G, Kapadia S, Kato T, Burton DR, et al. Robust hepatitis C virus infection in vitro. Proc Natl Acad Sci USA. 2005;102:9294–9299
  43. Pietschmann T, Kaul A, Koutsoudakis G, Shavinskaya A, Kallis S, Steinmann E, et al. Construction and characterization of infectious intragenotypic and intergenotypic hepatitis C virus chimeras. Proc Natl Acad Sci USA. 2006;103:7408–7413
  44. Yi M, Ma Y, Yates J, Lemon SM. Compensatory mutations in E1, p7, NS2, and NS3 enhance yields of cell culture-infectious intergenotypic chimeric hepatitis C virus. J Virol. 2007;81:629–638
  45. Steinmann E, Whitfield T, Kallis S, Dwek RA, Zitzmann N, Pietschmann T, et al. Antiviral effects of amantadine and iminosugar derivatives against hepatitis C virus. Hepatology. 2007;46:330–338
  46. Griffin S, St Gelais C, Owsianka A, Patel A, Rowlands D, Harris M. Genotype-dependent sensitivity of hepatitis C virus to inhibitors of the p7 ion channel. Hepatology, 2008 in press.

☆ P.T., N.P. and H.B. were employed by GlaxoSmithKline when this study was carried out. H.B. is currently employed by Pfizer Ltd., Sandwich, Kent, UK. S.G. is the recipient of an MRC New Investigator Award (G0700124). Other funding was provided by GlaxoSmithKline and the Wellcome Trust (Grant No. 074023).

PII: S0168-8278(08)00558-8

doi: 10.1016/j.jhep.2008.07.020

Journal of Hepatology
Volume 49, Issue 6 , Pages 908-915 , December 2008

Article Tools

* Image Usage & Resolution