1887

Abstract

GB virus type C (GBV-C) is a lymphotropic virus that can cause persistent infection in humans. GBV-C is not associated with any disease, but is associated with reduced mortality in human immunodeficiency virus type 1 (HIV-1)-infected individuals. Related viruses have been isolated from chimpanzees (GBV-Ccpz) and from New World primates (GB virus type A, GBV-A). These viruses are also capable of establishing persistent infection. We determined the nucleotide sequence encoding the envelope glycoprotein (E2) of two GBV-Ccpz isolates obtained from the sera of captive chimpanzees. The deduced GBV-Ccpz E2 protein differed from human GBV-C by 31 % at the amino acid level. Similar to human GBV-C E2, expression of GBV-Ccpz E2 in a tet-off human CD4 Jurkat T-cell line significantly inhibited the replication of diverse HIV-1 isolates. This anti-HIV-replication effect of GBV-Ccpz E2 protein was reversed by maintaining cells in doxycycline to reduce E2 expression. Previously, we found a 17 aa region within human GBV-C E2 that was sufficient to inhibit HIV-1. Although GBV-Ccpz E2 differed by 3 aa differences in this region, the chimpanzee GBV-C 17mer E2 peptide inhibited HIV-1 replication. Similarly, the GBV-A peptide that aligns with this GBV-C E2 region inhibited HIV-1 replication despite sharing only 5 aa with the human GBV-C E2 sequence. Thus, despite amino acid differences, the peptide region on both the GBV-Ccpz and the GBV-A E2 protein inhibit HIV-1 replication similar to human GBV-C. Consequently, GBV-Ccpz or GBV-A infection of non-human primates may provide an animal model to study GB virus–HIV interactions.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.047126-0
2013-04-01
2019-10-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/94/4/774.html?itemId=/content/journal/jgv/10.1099/vir.0.047126-0&mimeType=html&fmt=ahah

References

  1. Adams N. J., Prescott L. E., Jarvis L. M., Lewis J. C. M., McClure M. O., Smith D. B., Simmonds P.. ( 1998;). Detection in chimpanzees of a novel flavivirus related to GB virus-C/hepatitis G virus. . J Gen Virol 79:, 1871–1877.[PubMed]
    [Google Scholar]
  2. Alter H. J.. ( 1997;). G-pers creepers, where’d you get those papers? A reassessment of the literature on the hepatitis G virus. . Transfusion 37:, 569–572. [CrossRef][PubMed]
    [Google Scholar]
  3. Bhattarai N., Stapleton J. T.. ( 2012a;). GB virus C: the good boy virus?. Trends Microbiol 20:, 124–130. [CrossRef][PubMed]
    [Google Scholar]
  4. Bhattarai N., McLinden J. H., Xiang J., Kaufman T. M., Stapleton J. T.. ( 2012b;). GB virus C envelope protein E2 inhibits TCR-induced IL-2 production and alters IL-2-signaling pathways. . J Immunol 189:, 2211–2216. [CrossRef][PubMed]
    [Google Scholar]
  5. Birkenmeyer L. G., Desai S. M., Muerhoff A. S., Leary T. P., Simons J. N., Montes C. C., Mushahwar I. K.. ( 1998;). Isolation of a GB virus-related genome from a chimpanzee. . J Med Virol 56:, 44–51. [CrossRef][PubMed]
    [Google Scholar]
  6. Björkman P., Flamholc L., Molnegren V., Marshall A., Güner N., Widell A.. ( 2007;). Enhanced and resumed GB virus C replication in HIV-1-infected individuals receiving HAART. . AIDS 21:, 1641–1643. [CrossRef][PubMed]
    [Google Scholar]
  7. Blom N., Sicheritz-Pontén T., Gupta R., Gammeltoft S., Brunak S.. ( 2004;). Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence. . Proteomics 4:, 1633–1649. [CrossRef][PubMed]
    [Google Scholar]
  8. Bukh J., Kim J. P., Govindarajan S., Apgar C. L., Foung S. K., Wages J. Jr, Yun A. J., Shapiro M., Emerson S. U., Purcell R. H.. ( 1998;). Experimental infection of chimpanzees with hepatitis G virus and genetic analysis of the virus. . J Infect Dis 177:, 855–862. [CrossRef][PubMed]
    [Google Scholar]
  9. Fogeda M., Navas S., Martín J., Casqueiro M., Rodríguez E., Arocena C., Carreño V.. ( 1999;). In vitro infection of human peripheral blood mononuclear cells by GB virus C/hepatitis G virus. . J Virol 73:, 4052–4061.[PubMed]
    [Google Scholar]
  10. Fultz P. N., McClure H. M., Swenson R. B., McGrath C. R., Brodie A., Getchell J. P., Jensen F. C., Anderson D. C., Broderson J. R., Francis D. P.. ( 1986;). Persistent infection of chimpanzees with human T-lymphotropic virus type III/lymphadenopathy-associated virus: a potential model for acquired immunodeficiency syndrome. . J Virol 58:, 116–124.[PubMed]
    [Google Scholar]
  11. George S. L., Xiang J., Stapleton J. T.. ( 2003;). Clinical isolates of GB virus type C vary in their ability to persist and replicate in peripheral blood mononuclear cell cultures. . Virology 316:, 191–201. [CrossRef][PubMed]
    [Google Scholar]
  12. George S. L., Varmaz D., Stapleton J. T.. ( 2006;). GB virus C replicates in primary T and B lymphocytes. . J Infect Dis 193:, 451–454. [CrossRef][PubMed]
    [Google Scholar]
  13. Herrera E., Gomara M. J., Mazzini S., Ragg E., Haro I.. ( 2009;). 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 113:, 7383–7391. [CrossRef][PubMed]
    [Google Scholar]
  14. ICTV ( 2012;). Executive Committee Approved, Awaiting ICTV ratification. Available at: http://talk.ictvonline.org/search/default.aspx#q=Pegivirus
  15. Jung S., Eichenmüller M., Donhauser N., Neipel F., Engel A. M., Hess G., Fleckenstein B., Reil H.. ( 2007;). HIV entry inhibition by the envelope 2 glycoprotein of GB virus C. . AIDS 21:, 645–647. [CrossRef][PubMed]
    [Google Scholar]
  16. Larios C., Casas J., Alsina M. A., Mestres C., Gómara M. J., Haro I.. ( 2005;). Characterization of a putative fusogenic sequence in the E2 hepatitis G virus protein. . Arch Biochem Biophys 442:, 149–159. [CrossRef][PubMed]
    [Google Scholar]
  17. Maidana Giret M. T., Silva T. M., Sauer M. M., Tomiyama H., Levi J. E., Bassichetto K. C., Nishiya A., Diaz R. S., Sabino E. C.. & other authors ( 2009;). GB virus type C infection modulates T-cell activation independently of HIV-1 viral load. . AIDS 23:, 2277–2287. [CrossRef][PubMed]
    [Google Scholar]
  18. Mohr E. L., Stapleton J. T.. ( 2009;). GB virus type C interactions with HIV: the role of envelope glycoproteins. . J Viral Hepat 16:, 757–768. [CrossRef][PubMed]
    [Google Scholar]
  19. Mohr E. L., Xiang J., McLinden J. H., Kaufman T. M., Chang Q., Montefiori D. C., Klinzman D., Stapleton J. T.. ( 2010;). 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. . J Immunol 185:, 4496–4505. [CrossRef][PubMed]
    [Google Scholar]
  20. Mohr E. L., Murthy K. K., McLinden J. H., Xiang J., Stapleton J. T.. ( 2011;). The natural history of non-human GB virus C in captive chimpanzees. . J Gen Virol 92:, 91–100. [CrossRef][PubMed]
    [Google Scholar]
  21. Nattermann J., Nischalke H. D., Kupfer B., Rockstroh J., Hess L., Sauerbruch T., Spengler U.. ( 2003;). Regulation of CC chemokine receptor 5 in hepatitis G virus infection. . AIDS 17:, 1457–1462. [CrossRef][PubMed]
    [Google Scholar]
  22. NIH Webpage ( 2012;). NIH Research Involving Chimpanzees: Notice Number NOT-OD-12–025. Available at: grants.nih.gov/grants/guide/notice-files/NOT-OD-12-025.html
  23. Polgreen P. M., Xiang J., Chang Q., Stapleton J. T.. ( 2003;). GB virus type C/hepatitis G virus: a non-pathogenic flavivirus associated with prolonged survival in HIV-infected individuals. . Microbes Infect 5:, 1255–1261. [CrossRef][PubMed]
    [Google Scholar]
  24. Rey D., Vidinic-Moularde J., Meyer P., Schmitt C., Fritsch S., Lang J. M., Stoll-Keller F.. ( 2000;). High prevalence of GB virus C/hepatitis G virus RNA and antibodies in patients infected with human immunodeficiency virus type 1. . Eur J Clin Microbiol Infect Dis 19:, 721–724. [CrossRef][PubMed]
    [Google Scholar]
  25. Rydze R. T., Bhattarai N., Stapleton J. T.. ( 2012;). GB virus C infection is associated with a reduced rate of reactivation of latent HIV and protection against activation-induced T-cell death. . Antivir Ther 17:, 1271–1279. [CrossRef][PubMed]
    [Google Scholar]
  26. Schwarze-Zander C., Neibecker M., Othman S., Tural C., Clotet B., Blackard J. T., Kupfer B., Luechters G., Chung R. T.. & other authors ( 2010;). 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 15:, 745–752. [CrossRef][PubMed]
    [Google Scholar]
  27. Simons J. N., Pilot-Matias T. J., Leary T. P., Dawson G. J., Desai S. M., Schlauder G. G., Muerhoff A. S., Erker J. C., Buijk S. L., Chalmers M. L.. ( 1995;). Identification of two flavivirus-like genomes in the GB hepatitis agent. . Proc Natl Acad Sci U S A 92:, 3401–3405. [CrossRef][PubMed]
    [Google Scholar]
  28. Stapleton J. T.. ( 2003;). GB virus type C/hepatitis G virus. . Semin Liver Dis 23:, 137–148. [CrossRef][PubMed]
    [Google Scholar]
  29. Stapleton J. T., Foung S., Muerhoff A. S., Bukh J., Simmonds P.. ( 2011;). 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 92:, 233–246. [CrossRef][PubMed]
    [Google Scholar]
  30. Tillmann H. L., Heiken H., Knapik-Botor A., Heringlake S., Ockenga J., Wilber J. C., Goergen B., Detmer J., McMorrow M.. & other authors ( 2001;). Infection with GB virus C and reduced mortality among HIV-infected patients. . N Engl J Med 345:, 715–724. [CrossRef][PubMed]
    [Google Scholar]
  31. Xiang J., Wünschmann S., Schmidt W. N., Shao J., Stapleton J. T.. ( 2000;). Full-length GB virus C (Hepatitis G virus) RNA transcripts are infectious in primary CD4-positive T cells. . J Virol 74:, 9125–9133. [CrossRef][PubMed]
    [Google Scholar]
  32. Xiang J., Wünschmann S., Diekema D. J., Klinzman D., Patrick K. D., George S. L., Stapleton J. T.. ( 2001;). Effect of coinfection with GB virus C on survival among patients with HIV infection. . N Engl J Med 345:, 707–714. [CrossRef][PubMed]
    [Google Scholar]
  33. Xiang J., George S. L., Wünschmann S., Chang Q., Klinzman D., Stapleton J. T.. ( 2004;). Inhibition of HIV-1 replication by GB virus C infection through increases in RANTES, MIP-1α, MIP-1β, and SDF-1. . Lancet 363:, 2040–2046. [CrossRef][PubMed]
    [Google Scholar]
  34. Xiang J., McLinden J. H., Chang Q., Kaufman T. M., Stapleton J. T.. ( 2006;). An 85-aa segment of the GB virus type C NS5A phosphoprotein inhibits HIV-1 replication in CD4+ Jurkat T cells. . Proc Natl Acad Sci U S A 103:, 15570–15575. [CrossRef][PubMed]
    [Google Scholar]
  35. Xiang J., McLinden J. H., Chang Q., Jordan E. L., Stapleton J. T.. ( 2008;). Characterization of a peptide domain within the GB virus C NS5A phosphoprotein that inhibits HIV replication. . PLoS ONE 3:, e2580. [CrossRef][PubMed]
    [Google Scholar]
  36. Xiang J., McLinden J. H., Rydze R. A., Chang Q., Kaufman T. M., Klinzman D., Stapleton J. T.. ( 2009;). Viruses within the Flaviviridae decrease CD4 expression and inhibit HIV replication in human CD4+ cells. . J Immunol 183:, 7860–7869. [CrossRef][PubMed]
    [Google Scholar]
  37. Xiang J., McLinden J. H., Kaufman T. M., Mohr E. L., Bhattarai N., Chang Q., Stapleton J. T.. ( 2012;). Characterization of a peptide domain within the GB virus C envelope glycoprotein (E2) that inhibits HIV replication. . Virology 430:, 53–62. [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.047126-0
Loading
/content/journal/jgv/10.1099/vir.0.047126-0
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error