1887

Abstract

GB virus type C (GBV-C) is a common human flavivirus that has been associated with prolonged survival in HIV-positive individuals in several, though not all, epidemiological studies. There are five distinct GBV-C genotypes that are geographically localized, and it has been speculated that GBV-C genotypic differences may explain variable outcomes observed in different clinical studies. Expression of an 85 aa fragment of the GBV-C NS5A phosphoprotein (genotype 2) in a CD4 T cell line (Jurkat) resulted in inhibition of HIV replication, mediated in part by decreased surface expression of the HIV coreceptor CXCR4 and upregulation of SDF-1. We expressed the NS5A protein from genotypes 1, 2, 3 and 5 in Jurkat cells, and demonstrated that all genotypes inhibited HIV replication. Further deletion mapping demonstrated that expression of a 30 aa fragment resulted in decreased CXCR4 surface expression, upregulation of SDF-1 and inhibition of HIV replication.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.83198-0
2007-12-01
2020-10-30
Loading full text...

Full text loading...

/deliver/fulltext/jgv/88/12/3341.html?itemId=/content/journal/jgv/10.1099/vir.0.83198-0&mimeType=html&fmt=ahah

References

  1. 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]
    [Google Scholar]
  2. Amella C. A., Sherry B., Shepp D. H., Schmidtmayerova H. 2005; Macrophage inflammatory protein 1 α inhibits postentry steps of human immunodeficiency virus type 1 infection via suppression of intracellular cyclic AMP. J Virol 79:5625–5631 [CrossRef]
    [Google Scholar]
  3. Birk M., Lindback S., Lidman C. 2002; No influence of GB virus C replication on the prognosis in a cohort of HIV-1-infected patients. AIDS 16:2482–2485 [CrossRef]
    [Google Scholar]
  4. Bjorkman P., Flamholc L., Naucler A., Molnegren V., Wallmark E., Widell A. 2004; GB virus C during the natural course of HIV-1 infection: viremia at diagnosis does not predict mortality. AIDS 18:877–886 [CrossRef]
    [Google Scholar]
  5. Cocchi F., DeVico A. L., Garzino-Demo A., Arya S. K., Gallo R. C., Lusso P. 1995; Identification of RANTES, MIP-1a, and MIP-1b as the major HIV-suppressive factors produced by CD8+ T cells. Science 270:1811–1815 [CrossRef]
    [Google Scholar]
  6. Copeland K. F. 2005; Modulation of HIV-1 transcription by cytokines and chemokines. Mini Rev Med Chem 5:1093–1101 [CrossRef]
    [Google Scholar]
  7. 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]
    [Google Scholar]
  8. Jung S., Knauer O., Donhauser N., Eichenmuller M., Helm M., Fleckenstein B., Reil H. 2005; Inhibition of HIV strains by GB virus C in cell culture can be mediated by CD4 and CD8 T-lymphocyte derived soluble factors. AIDS 19:1267–1272 [CrossRef]
    [Google Scholar]
  9. Jung S., Eichenmueller 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]
    [Google Scholar]
  10. Leary T. P., Muerhoff A. S., Simons J. N., Pilot-Matias T. J., Erker J. C., Chalmers M. L., Schlauder G. G., Dawson G. J., Desai S. M., Mushahwar I. K. 1996; Sequence and genomic organization of GBV-C: a novel member of the Flaviviridae associated with human non-A-E hepatitis. J Med Virol 48:60–67 [CrossRef]
    [Google Scholar]
  11. Lin Y. L., Mettling C., Portales P., Reynes J., Clot J., Corbeau P. 2002; Cell surface CCR5 density determines the postentry efficiency of R5 HIV-1 infection. Proc Natl Acad Sci U S A 99:15590–15595 [CrossRef]
    [Google Scholar]
  12. Linnen J., Wages J., Zhang-Keck Z.-Y., Fry K. E., Krawczynski K. Z., Alter H., Koonin E., Gallagher M., Alter M. other authors 1996; Molecular cloning and disease association of hepatitis G virus: a transfusion-transmissible agent. Science 271:505–508 [CrossRef]
    [Google Scholar]
  13. Macdonald A., Harris M. 2004; Hepatitis C virus NS5A: tales of a promiscuous protein. J Gen Virol 85:2485–2502 [CrossRef]
    [Google Scholar]
  14. Muerhoff A. S., Tillmann H. L., Manns M., Dawson G. J., Desai S. M. 2003; GB virus C genotype determination in GB virus-C/HIV co-infected individuals. J Med Virol 70:141–149 [CrossRef]
    [Google Scholar]
  15. 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]
    [Google Scholar]
  16. Polgreen P. M., Xiang J., Chang Q., Stapleton J. T. 2003; GB virus type C/hepatitis G virus: a nonpathogenic flavivirus associated with prolonged survival in HIV-infected individuals. Microbes Infect 5:1255–1261 [CrossRef]
    [Google Scholar]
  17. Schwarze-Zander C., Blackard J. T., Zheng H., Addo M. M., Lin W., Robbins G. K., Sherman K. E., Zdunek D., Hess G. other authors 2006; GB virus C (GBV-C) infection in hepatitis C virus (HCV)/HIV-coinfected patients receiving HCV treatment: importance of the GBV-C genotype. J Infect Dis 194:410–419 [CrossRef]
    [Google Scholar]
  18. Simons J. N., Leary T. P., Dawson G. J., Pilot-Matias T. J., Muerhoff A. S., Schlauder G. G., Desai S. M., Mushahwar I. K. 1995; Isolation of novel virus-like sequences associated with human hepatitis. Nat Med 1:564–569 [CrossRef]
    [Google Scholar]
  19. Smith D. B., Cuceanu N., Davidson F., Jarvis L. M., Mokili J. L., Hamid S., Ludlam C. A., Simmonds P. 1997; Discrimination of hepatitis G virus/GBV-C geographical variants by analysis of the 5′ non-coding region. J Gen Virol 78:1533–1542
    [Google Scholar]
  20. Stapleton J. T. 2003; GB virus type C/hepatitis G virus. Semin Liver Dis 23:137–148 [CrossRef]
    [Google Scholar]
  21. Stapleton J. T., Williams C. F., Xiang J. 2004; GB virus C: a beneficial infection?. J Clin Microbiol 42:3915–3919 [CrossRef]
    [Google Scholar]
  22. Van der Bij A. K., Kloosterboer N., Prins M., Boeser-Nunnink B., Geskus R. B., Lange J. M. A., Coutinho R. A., Schuitemaker H. 2005; GB virus C coinfection and HIV-1 disease progression: the Amsterdam cohort study. J Infect Dis 191:678–685 [CrossRef]
    [Google Scholar]
  23. Williams C. F., Klinzman D., Yamashita T. E., Xiang J., Polgreen P. M., Rinaldo C., Liu C., Phair J., Margolick J. B. other authors 2004; Persistent GB virus C infection and survival in HIV-infected men. N Engl J Med 350:981–990 [CrossRef]
    [Google Scholar]
  24. Xiang J., Wunschmann 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]
    [Google Scholar]
  25. Xiang J., Wunschmann S., Diekema D. J., Klinzman D., Patrick K. D., George S. L., Stapleton J. T. 2001; Effect of coinfection with GB virus C (hepatitis G virus) on survival among patients with HIV infection. N Engl J Med 345:707–714 [CrossRef]
    [Google Scholar]
  26. Xiang J., George S. L., Wunschmann S., Chang Q., Klinzman D., Stapleton J. T. 2004; Inhibition of HIV-1 replication by GB virus C infection through increases in RANTES, MIP-1 α , MIP-1 β , and SDF-1. Lancet 363:2040–2046 [CrossRef]
    [Google Scholar]
  27. Xiang J., Martinez-Smith C., Gale M. Jr, LaBrecque D. R., Schmidt W. N., Stapleton J. T. 2005a; GB virus C NS5A sequence polymorphisms: association with interferon susceptibility and inhibition of PKR-mediated eIF-2 α phosphorylation. J Interferon Cytokine Res 25:261–270 [CrossRef]
    [Google Scholar]
  28. Xiang J., Sathar M. A., McLinden J. H., Klinzman D., Chang Q., Stapleton J. T. 2005b; South African GB virus C isolates: interactions between genotypes 1 and 5 GBV-C isolates and the human immunodeficiency virus. J Infect Dis 192:2147–2151 [CrossRef]
    [Google Scholar]
  29. 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]
    [Google Scholar]
  30. Zhang W., Chaloner K., Tillmann H. L., Williams C. F., Stapleton J. T. 2006; Effect of early and late GBV-C viremia on survival of HIV infected individuals: a meta-analysis. HIV Med 7:173–180 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.83198-0
Loading
/content/journal/jgv/10.1099/vir.0.83198-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

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