Current HIV/AIDS Reports

, Volume 9, Issue 1, pp 26–33

GBV-C: State of the Art and Future Prospects

  • Maria Teresa Maidana Giret
  • Esper Georges Kallas
The Science of HIV (AL Landay, Section Editor)

Abstract

The GB virus C is a common non-pathogenic virus, member of the Flaviviridae family with worldwide distribution. Favorable clinical course and reduced mortality among HIV-infected patients was demonstrated by several studies with patients co-infected with the GB virus C (GBV-C). This potential benefit of GBV-C has been demonstrated in the pre-HAART and post-HAART eras; however, this effect was not observed in all studies and the discrepancy may be due to changes during the course of HIV infection, characteristic of the cohort, and the degree of therapeutic response. The GBV-C has been found to decrease HIV replication in in vitro models, highlighting the interference of persistent GBV-C viremia. The mechanism of the beneficial effect of GBV-C appears to be mediated by changes in the cellular immune response, and elucidation of putative protective effects of GBV-C in HIV co-infection could potentially identify novel targets for anti-HIV agents.

Keywords

Human immunodeficiency virus (HIV) GB virus C (GBV-C) Co-infection Activation Inhibition 

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    Linnen J, Wages Jr J, Zhang-Keck ZY, et al. Molecular cloning and disease association of hepatitis G virus: a transfusion-transmissible agent. Science. 1996;271:505–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Simons JN, Leary TP, Dawson GJ, et al. Isolation of novel virus-like sequences associated with human hepatitis. Nat Med. 1995;1:564–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Stapleton JT, Foung S, Muerhoff AS, et al. The GB viruses: a review and proposed classification of GBV-A, GBV-C (HGV), and GBV-D in genus pegivirus within the family Flaviviridae. J Gen Virol. 2011;92:233–46.PubMedCrossRefGoogle Scholar
  4. 4.
    Ruiz V, Giordano M, Rivero CW, et al. GB virus C quasispecies detected in plasma and lymphocyte subsets in a natural human infection. J Gen Virol. 2010;91:1687–92.PubMedCrossRefGoogle Scholar
  5. 5.
    Mohr EL, Murthy KK, McLinden JH, et al. The natural history of non-human GB virus C in captive chimpanzees. J Gen Virol. 2011;92:91–100.PubMedCrossRefGoogle Scholar
  6. 6.
    Alvarado-Mora MV, Botelho L, Nishiya A, et al. Frequency and genotypic distribution of GB virus C (GBV-C) among Colombian population with hepatitis B (HBV) or hepatitis C (HCV) infection. Virol J. 2011;8:345.PubMedCrossRefGoogle Scholar
  7. 7.
    Giret MT, Miraglia JL, Sucupira MC, et al. Prevalence, incidence density, and genotype distribution of GB virus C infection in a cohort of recently HIV-1-infected subjects in Sao Paulo, Brazil. PLoS One. 2011;6:e18407.PubMedCrossRefGoogle Scholar
  8. 8.
    Branco C, Esteves A, Piedade J, et al. A new genotype 2 subcluster identified among GBV-C strains circulating in the Lisbon metropolitan area of Portugal. J Med Virol. 2010;82:452–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Gomara MJ, Fernandez L, Perez T, et al. Assessment of synthetic chimeric multiple antigenic peptides for diagnosis of GB virus C infection. Anal Biochem. 2010;396:51–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Gomara MJ, Fernandez L, Perez T, et al. Diagnostic value of anti-GBV-C antibodies in HIV-infected patients. Chem Biol Drug Des. 2011;78:277–82.PubMedCrossRefGoogle Scholar
  11. 11.
    Lefrere JJ, Roudot-Thoraval F, Morand-Joubert L, et al. Carriage of GB virus C/hepatitis G virus RNA is associated with a slower immunologic, virologic, and clinical progression of human immunodeficiency virus disease in coinfected persons. J Infect Dis. 1999;179:783–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Tillmann HL, Heiken H, Knapik-Botor A, et al. Infection with GB virus C and reduced mortality among HIV-infected patients. N Engl J Med. 2001;345:715–24.PubMedCrossRefGoogle Scholar
  13. 13.
    Xiang J, Wunschmann S, Diekema DJ, et al. Effect of coinfection with GB virus C on survival among patients with HIV infection. N Engl J Med. 2001;345:707–14.PubMedCrossRefGoogle Scholar
  14. 14.
    Yeo AE, Matsumoto A, Hisada M, et al. Effect of hepatitis G virus infection on progression of HIV infection in patients with hemophilia. Multicenter hemophilia cohort study. Ann Intern Med. 2000;132:959–63.PubMedGoogle Scholar
  15. 15.
    Williams CF, Klinzman D, Yamashita TE, et al. Persistent GB virus C infection and survival in HIV-infected men. N Engl J Med. 2004;350:981–90.PubMedCrossRefGoogle Scholar
  16. 16.
    Nunnari G, Nigro L, Palermo F, et al. Slower progression of HIV-1 infection in persons with GB virus C co-infection correlates with an intact T-helper 1 cytokine profile. Ann Intern Med. 2003;139:26–30.PubMedGoogle Scholar
  17. 17.
    Hekmat S, Mohraz M, Vahabpour R, et al. Frequency and genotype of GB virus C among Iranian patients infected with HIV. J Med Virol. 2008;80:1941–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Campos AF, Tengan FM, Silva SA, et al. Influence of hepatitis G virus (GB virus C) on the prognosis of HIV-infected women. Int J STD AIDS. 2011;22:209–13.PubMedCrossRefGoogle Scholar
  19. 19.
    Neibecker M, Schwarze-Zander C, Rockstroh JK, et al. Evidence for extensive genotypic diversity and recombination of GB virus C (GBV-C) in Germany. J Med Virol. 2011;83:685–94.PubMedCrossRefGoogle Scholar
  20. 20.
    Compston LI, Li C, Sarkodie F, et al. Prevalence of persistent and latent viruses in untreated patients infected with HIV-1 from Ghana, West Africa. J Med Virol. 2009;81:1860–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Ramezani A, Gachkar L, Eslamifar A, et al. Detection of hepatitis G virus envelope protein E2 antibody in blood donors. Int J Infect Dis: IJID: Off Publ Int Soc Infect Dis. 2008;12:57–61.Google Scholar
  22. 22.
    Ramezani A, Mohraz M, Vahabpour R, et al. Frequency of hepatitis G virus infection among HIV positive subjects with parenteral and sexual exposure. J Gastrointestin Liver Dis. 2008;17:269–72.PubMedGoogle Scholar
  23. 23.
    Hosseini-Moghaddam SM, Keyvani H, Samadi M, et al. GB virus type C infection in hemodialysis patients considering co-infection with hepatitis C virus. J Med Virol. 2008;80:1260–3.PubMedCrossRefGoogle Scholar
  24. 24.
    Bhanich Supapol W, Remis RS, Raboud J, et al. Prevalence and correlates of GB virus C infection in HIV-infected and HIV-uninfected pregnant women in Bangkok, Thailand. J Med Virol. 2011;83:33–44.PubMedCrossRefGoogle Scholar
  25. 25.
    Supapol WB, Remis RS, Raboud J, et al. Reduced mother-to-child transmission of HIV associated with infant but not maternal GB virus C infection. J Infect Dis. 2008;197:1369–77.PubMedCrossRefGoogle Scholar
  26. 26.
    Hammad AM, Zaghloul MH. Hepatitis G virus infection in Egyptian children with chronic renal failure (single centre study). Ann Clin Microbiol Antimicrob. 2009;8:36.PubMedCrossRefGoogle Scholar
  27. 27.
    Xiang J, McLinden JH, Rydze RA, et al. Viruses within the Flaviviridae decrease CD4 expression and inhibit HIV replication in human CD4+ cells. J Immunol. 2009;183:7860–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Van der Bij AK, Kloosterboer N, Prins M, et al. GB virus C coinfection and HIV-1 disease progression: the Amsterdam cohort study. J Infect Dis. 2005;191:678–85.PubMedCrossRefGoogle Scholar
  29. 29.
    Maidana-Giret MT, Silva TM, Sauer MM, et al. GB virus type C infection modulates T-cell activation independently of HIV-1 viral load. AIDS. 2009;23:2277–87.PubMedCrossRefGoogle Scholar
  30. 30.
    Stapleton JT, Chaloner K, Zhang J, et al. GBV-C viremia is associated with reduced CD4 expansion in HIV-infected people receiving HAART and interleukin-2 therapy. Aids 2009.Google Scholar
  31. 31.
    Blankson JN, Klinzman D, Astemborski J, et al. Low frequency of GB virus C viremia in a cohort of HIV-1-infected elite suppressors. AIDS. 2008;22:2398–400.PubMedCrossRefGoogle Scholar
  32. 32.
    Schwarze-Zander C, Neibecker M, Othman S, et al. GB virus C coinfection in advanced HIV type-1 disease is associated with low CCR5 and CXCR4 surface expression on CD4(+) T-cells. Antivir Ther. 2010;15:745–52.PubMedCrossRefGoogle Scholar
  33. 33.
    Barbosa Ade J, Baggio-Zappia GL, Dobo C, et al. Analysis of GB virus C infection among HIV-HCV coinfected patients. Rev Soc Bras Med Trop. 2009;42:591–3.PubMedCrossRefGoogle Scholar
  34. 34.
    Boodram B, Hershow RC, Klinzman D, et al. GB virus C infection among young, HIV-negative injection drug users with and without hepatitis C virus infection. J Viral Hepat. 2011;18:e153–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Hofer H, Aydin I, Neumueller-Guber S, et al. Prevalence and clinical significance of GB virus type C/hepatitis G virus coinfection in patients with chronic hepatitis C undergoing antiviral therapy. J Viral Hepat. 2011;18:513–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Berzsenyi MD, Woollard DJ, McLean CA, et al. Down-regulation of intra-hepatic T-cell signaling associated with GB virus C in a HCV/HIV co-infected group with reduced liver disease. J Hepatol 2011.Google Scholar
  37. 37.
    Lalle E, Sacchi A, Abbate I, et al. Activation of interferon response genes and of plasmacytoid dendritic cells in HIV-1 positive subjects with GB virus C co-infection. Int J Immunopathol Pharmacol. 2008;21:161–71.PubMedGoogle Scholar
  38. 38.
    Moenkemeyer M, Schmidt RE, Wedemeyer H, et al. GBV-C coinfection is negatively correlated to Fas expression and Fas-mediated apoptosis in HIV-1 infected patients. J Med Virol. 2008;80:1933–40.PubMedCrossRefGoogle Scholar
  39. 39.
    Xiang J, McLinden JH, Chang Q, et al. Characterization of a peptide domain within the GB virus C NS5A phosphoprotein that inhibits HIV replication. PLoS One. 2008;3:e2580.PubMedCrossRefGoogle Scholar
  40. 40.
    McLinden JH, Stapleton JT, Chang Q, et al. Expression of the dengue virus type 2 NS5 protein in a CD4(+) T cell line inhibits HIV replication. J Infect Dis. 2008;198:860–3.PubMedCrossRefGoogle Scholar
  41. 41.
    •• Mohr EL, Xiang J, McLinden JH, et al. GB virus type C envelope protein E2 elicits antibodies that react with a cellular antigen on HIV-1 particles and neutralize diverse HIV-1 isolates. Journal of immunology 2010, 185: 4496-4505. This study indicates that the GBV-C E2 protein has a structural motif that elicits Abs that cross-react with a cellular Ag present on retrovirus particles, independent of HIV-1 envelope glycoproteins. The data provide evidence that a heterologous viral protein can induce HIV-1–neutralizing Abs. PubMedCrossRefGoogle Scholar
  42. 42.
    Perez-Lopez S, Vila-Romeu N, Alsina Esteller MA, et al. Interaction of GB Virus C/Hepatitis G Virus Synthetic Peptides with Lipid Langmuir Monolayers and Large Unilamellar Vesicles. J Phys Chem B 2008.Google Scholar
  43. 43.
    Sanchez-Martin MJ, Amigo JM, Pujol M, et al. Fluorescence study of the dynamic interaction between E1(145-162) sequence of hepatitis GB virus C and liposomes. Anal Bioanal Chem. 2009;394:1003–10.PubMedCrossRefGoogle Scholar
  44. 44.
    Perez-Lopez S, Nieto-Suarez M, Mestres C, et al. Behaviour of a peptide sequence from the GB virus C/hepatitis G virus E2 protein in Langmuir monolayers: its interaction with phospholipid membrane models. Biophys Chem. 2009;141:153–61.PubMedCrossRefGoogle Scholar
  45. 45.
    Herrera E, Gomara MJ, Mazzini S, et al. Synthetic peptides of hepatitis G virus (GBV-C/HGV) in the selection of putative peptide inhibitors of the HIV-1 fusion peptide. J Phys Chem B. 2009;113:7383–91.PubMedCrossRefGoogle Scholar
  46. 46.
    Haro I, Gomara MJ, Galatola R, et al. Study of the inhibition capacity of an 18-mer peptide domain of GBV-C virus on gp41-FP HIV-1 activity. Biochim Biophys Acta. 2011;1808:1567–73.PubMedCrossRefGoogle Scholar
  47. 47.
    Koedel Y, Eissmann K, Wend H, et al. Peptides derived from a distinct region of GB virus C glycoprotein E2 mediate strain-specific HIV-1 entry inhibition. J Virol. 2011;85:7037–47.PubMedCrossRefGoogle Scholar
  48. 48.
    Sanchez-Martin MJ, Hristova K, Pujol M, et al. Analysis of HIV-1 fusion peptide inhibition by synthetic peptides from E1 protein of GB virus C. J Colloid Interface Sci. 2011;360:124–31.PubMedCrossRefGoogle Scholar
  49. 49.
    Sanchez-Martin MJ, Busquets MA, Girona V, et al. Effect of E1(64-81) hepatitis G peptide on the in vitro interaction of HIV-1 fusion peptide with membrane models. Biochim Biophys Acta. 2011;1808:2178–88.PubMedCrossRefGoogle Scholar
  50. 50.
    Sanchez-Martin MJ, Urban P, Pujol M, et al. Biophysical Investigations of GBV-C E1 Peptides as Potential Inhibitors of HIV-1 Fusion Peptide. Chemphyschem : a European journal of chemical physics and physical chemistry 2011.Google Scholar
  51. 51.
    Herrera E, Tenckhoff S, Gomara MJ, et al. Effect of synthetic peptides belonging to E2 envelope protein of GB virus C on human immunodeficiency virus type 1 infection. J Med Chem. 2010;53:6054–63.PubMedCrossRefGoogle Scholar
  52. 52.
    Stapleton JT, Chaloner K, Zhang J, et al. GBV-C viremia is associated with reduced CD4 expansion in HIV-infected people receiving HAART and interleukin-2 therapy. AIDS. 2009;23:605–10.PubMedCrossRefGoogle Scholar
  53. 53.
    Mohr EL, Stapleton JT. GB virus type C interactions with HIV: the role of envelope glycoproteins. J Viral Hepat. 2009;16:757–68.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Maria Teresa Maidana Giret
    • 1
  • Esper Georges Kallas
    • 1
  1. 1.Division of Clinical Immunology and Allergy, School of MedicineUniversity of São PauloSão PauloBrazil

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