1887

Abstract

In order to investigate hepatitis C virus (HCV) persistence and replication in peripheral blood mononuclear cells (PBMC) from a group of haemophilic individuals, HCV production and release to PBMC culture supernatants (SNs) from HCV singly infected patients and HIV/HCV co-infected patients was studied. HCV RNA SNs were found more frequently from HIV/HCV co-infected individuals (89·5 %) with poor reconstitution of their immune status than from singly HCV-infected patients (57 %) or from HIV/HCV co-infected individuals with a good response to highly active anti-retroviral therapy (50 %). The presence of the HCV genome in culture SNs was associated with lower CD4 T-cell counts and with a more severe clinical picture of HIV infection. In spite of prolonged negative HCV viraemia, PBMC from HIV/HCV co-infected patients released the HCV genome after culture. HCV permissive PBMC allowed generation of HCV productive B cell lines with continuous HCV replication. These findings add further weight to the involvement of PBMCs in persistence of HCV infection and emphasize the role of B lymphocytes as HCV reservoirs.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80882-0
2005-06-01
2020-05-26
Loading full text...

Full text loading...

/deliver/fulltext/jgv/86/6/vir861717.html?itemId=/content/journal/jgv/10.1099/vir.0.80882-0&mimeType=html&fmt=ahah

References

  1. Baré P., Massud I., Belmonte L., Corti M., Villafane M., Perez Bianco R., de Tezanos-pinto M., de Bracco M. M., Ruibal Ares B. 2003; HCV recovery from peripheral blood mononuclear cell culture supernatants derived from HCV-HIV co-infected hemophilic patients with undetectable HCV viraemia. Haemophilia 9:598–604 [CrossRef]
    [Google Scholar]
  2. Beld M., Penning M., Lukashov V., McMorrow M., Roos M., Pakker N., van den Hoek A., Goudsmit J. 1998; Evidence that both HIV and HIV-induced immunodeficiency enhance HCV replication among HCV seroconverters. Virology 244:504–512 [CrossRef]
    [Google Scholar]
  3. Belmonte L., Baré P., Picchio G. R., Pérez Bianco R., de Tezanos Pinto M., Corti M., Villafañe M. F., de Bracco M. M., Ruibal Ares B. H. 2002; Decreased recovery of replication-competent HIV-1 from peripheral blood mononuclear cell-derived monocyte/macrophages of HIV-positive patients after 3 years on highly active antiretroviral therapy. AIDS 16:1289–1292 [CrossRef]
    [Google Scholar]
  4. Boisvert J., He X. S., Cheung R., Keeffe E. B., Wright T., Greenberg H. B. 2001; Quantitative analysis of hepatitis C virus in peripheral blood and liver: replication detected only in liver. J Infect Dis 184:827–835 [CrossRef]
    [Google Scholar]
  5. Bonacini M., Govindarajan S., Blatt L. M., Schmid P., Conrad A., Lindsay K. L. 1999; Patients co-infected with human immunodeficiency virus and hepatitis C virus demonstrate higher levels of hepatic HCV RNA. J Viral Hepat 6:203–208 [CrossRef]
    [Google Scholar]
  6. Caussin-Schwemling C., Schmitt C., Stoll-Keller F. 2001; Study of infection of human blood derived monocyte/macrophages with hepatitis C virus in vitro. J Med Virol 65:14–22 [CrossRef]
    [Google Scholar]
  7. Daar E. S., Lynn H., Donfield S. 7 other authors 2001; Relation between HIV-1 and hepatitis C viral load in patients with hemophilia. J Acquir Immune Defic Syndr 26:466–472 [CrossRef]
    [Google Scholar]
  8. Davidson F., Simmonds P., Ferguson J. C. 19 other authors 1995; Survey of major genotypes and subtypes of hepatitis C virus using RFLP of sequences amplified from the 5′ non-coding region. J Gen Virol 76:1197–1204 [CrossRef]
    [Google Scholar]
  9. Eyster M. E., Fried M., Di Bisceglie A. M., Goedert J. J. 1994; Increasing hepatitis C virus RNA levels in hemophiliacs: relationship to human immunodeficiency virus infection and liver disease. Blood 84:1020–1023
    [Google Scholar]
  10. Felsenstein J. 1993 phylip – Phylogenetic Interference Package Version 3.5 Department of Genetics, University of Washington; Seattle USA:
    [Google Scholar]
  11. Giannini C., Caini P., Giannelli F., Fontana F., Kremsdorf D., Brechot C., Zignego A. L. 2002; Hepatitis C virus core protein expression in human B-cell lines does not significantly modify main proliferative and apoptosis pathways. J Gen Virol 83:1665–1671
    [Google Scholar]
  12. Hu Y., Shahidi A., Park S., Guilfoyle D., Hirshfield I. 2003; Detection of extrahepatic hepatitis C virus replication by a novel, highly sensitive, single-tube nested polymerase chain reaction. Am J Clin Pathol 119:95–100 [CrossRef]
    [Google Scholar]
  13. Kim A. Y., Lauer G. M., Ouchi K. 12 other authors 2005; The magnitude and breadth of hepatitis C virus-specific CD8+ T cells depend on absolute CD4+ T cell count in HIV-1 coinfected individuals. Blood 105:1170–1178
    [Google Scholar]
  14. Laskus T., Radkowski M., Piasek A., Nowicki M., Horban A., Cianciara J., Rakela J. 2000; Hepatitis C virus in lymphoid cells of patients coinfected with human immunodeficiency virus type 1: evidence of active replication in monocytes/macrophages and lymphocytes. J Infect Dis 181:442–448 [CrossRef]
    [Google Scholar]
  15. Laskus T., Radkowski M., Jablonska J., Kibler K., Wilkinson J., Adair D., Rakela J. 2004; Human immunodeficiency virus facilitates infection/replication of hepatitis C virus in native human macrophages. Blood 103:3854–3859 [CrossRef]
    [Google Scholar]
  16. Lérat H., Rumin S., Habersetzer F., Berby F., Trabaud M. A., Trépo C., Inchauspe G. 1998; In vivo tropism of hepatitis C virus genomic sequences in hematopoietic cells: influence of viral load, viral genotype, and cell phenotype. Blood 91:3841–3849
    [Google Scholar]
  17. Moldvay J., Deny P., Pol S., Bréchot C., Lamas E. 1994; Detection of hepatitis C RNA in peripheral blood mononuclear cells of infected patients by in situ hybridization. Blood 83:269–273
    [Google Scholar]
  18. Nikiforow S., Bottomly K., Miller G. 2001; CD4+ T-cell effectors inhibit Epstein-Barr virus-induced B-cell proliferation. J Virol 75:3740–3752 [CrossRef]
    [Google Scholar]
  19. Pham T. N., MacParland S. A., Mulrooney P. M., Cooksley H., Naoumov N. V., Michalak T. I. 2004; Hepatitis C virus persistence after spontaneous or treatment-induced resolution of hepatitis C. J Virol 78:5867–5874 [CrossRef]
    [Google Scholar]
  20. Radkowski M., Gallegos-Orozco J. F., Jablonska J. 7 other authors 2005; Persistence of hepatitis C virus in patients successfully treated for chronic hepatitis C. Hepatology 41:106–114 [CrossRef]
    [Google Scholar]
  21. Rodríguez-Iñigo E., Casqueiro M., Navas S., Bartolomé J., Pardo M., Carreno V. 2000; Fluorescent “in situ” hybridization of hepatitis C virus RNA in peripheral blood mononuclear cells from patients with chronic hepatitis C. J Med Virol 60:269–274 [CrossRef]
    [Google Scholar]
  22. Ruibal-Ares B., Riera N. E., Bracco M. M. E. 1997; Macrophages, multinucleated giant cells, and apoptosis in HIV+ patients and normal blood donors. Clin Immunol Immunopathol 82:102–116 [CrossRef]
    [Google Scholar]
  23. Ruibal-Ares B., Belmonte L., Baré P., Bayo-Hanza C., Mendez G., Bianco R. P., de Tezanos Pinto M., de Bracco M. M. E. 2001a; Monocyte differentiation and HIV replication after prolonged culture of peripheral blood mononuclear cells from HIV-infected individuals. Cell Immunol 210:11–20 [CrossRef]
    [Google Scholar]
  24. Ruibal-Ares B., Belmonte L., Baré P., Scolnik M., Palacios M. F., Bayo-Hanza C., Galmarini C. M., Mendez G., de Bracco M. M. 2001b; Immortalized Epstein-Barr virus-positive B-cell lines obtained by prolonged culture of peripheral blood mononuclear cells from human immunodeficiency virus type-1 positive patients. J Hum Virol 4:200–213
    [Google Scholar]
  25. Sung V. M., Shimodaira S., Doughty A. L., Picchio G. R., Can H., Yen T. S., Lindsay K. L., Levine A. M., Lai M. M. 2003; Establishment of B-cell lymphoma cell lines persistently infected with hepatitis C virus in vivo and in vitro: the apoptotic effects of virus infection. J Virol 77:2134–2146 [CrossRef]
    [Google Scholar]
  26. Thomas D. L., Astemborski J., Vlahov D. 7 other authors 2000; Determinants of the quantity of hepatitis C virus RNA. J Infect Dis 181:844–851 [CrossRef]
    [Google Scholar]
  27. Thompson J. D., Gibson T. J., Plewniak F., Jeanmougin F., Higgins D. G. 1997; The clustal_x windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25:4876–4882 [CrossRef]
    [Google Scholar]
  28. Torres B., Martin J. L., Caballero A., Villalobos M., Olea N. 2000; HCV in serum, peripheral blood mononuclear cells and lymphocyte subpopulations in C-hepatitis patients. Hepatol Res 18:141–151 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.80882-0
Loading
/content/journal/jgv/10.1099/vir.0.80882-0
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