1887

Abstract

Hepatitis C virus (HCV) has been reported to replicate in monocytes/macrophages in infected patients. However, it is unclear whether macrophages are susceptible to infection and whether such an infection is consequential. Sera from 26 HCV-infected patients were incubated with primary human macrophages collected from healthy donors. Virus negative strand was detected by a enzyme-based strand-specific assay and virus sequences were analysed by single strand conformation polymorphism (SSCP) and sequencing. Concentrations of the cytokines tumour necrosis factor- (TNF-) and interleukin (IL)-1, IL-6, IL-8, IL-10 and IL-12p70 were measured in culture supernatants and respective mRNAs were analysed in cell extracts by quantitative RT-PCR. For 15 sera, HCV RNA was detectable in 2- and 3-week cultures from at least one donor. Virus negative strand was detected in 29 % of macrophage samples in this group. In four cases, HCV RNA sequences amplified from macrophages differed from those amplified from sera suggesting evolution during infection. Concentrations of TNF- and IL-8 were found to be significantly higher in supernatants from HCV-infected cultures. In conclusion, these preliminary data suggest that primary human macrophages are susceptible to HCV infection and this infection is associated with the induction of cytokines TNF- and IL-8.

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2004-01-01
2019-10-16
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References

  1. Auffermann-Gretzinger, S., Keeffe, E. B. & Levy, S. ( 2001; ). Impaired dendritic cell maturation in patients with chronic, but not resolved, hepatitis C virus infection. Blood 97, 3171–3176.[CrossRef]
    [Google Scholar]
  2. Bain, C., Fatmi, A., Zoulim, F., Zarski, J. P., Trepo, C. & Inchauspe, G. ( 2001; ). Impaired allostimulatory function of dendritic cells in chronic hepatitis C infection. Gastroenterology 120, 512–524.[CrossRef]
    [Google Scholar]
  3. Becker, S., Quay, J. & Soukup, J. ( 1991; ). Cytokine (tumor necrosis factor, IL-6, and IL-8) production by respiratory syncytial virus-infected human alveolar macrophages. J Immunol 147, 4307–4312.
    [Google Scholar]
  4. 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]
  5. Bronowicki, J. P., Loriot, M. A., Thiers, V., Grignon, Y., Zignego, A. L. & Brechot, C. ( 1998; ). Hepatitis C virus persistence in human hematopoietic cells injected into SCID mice. Hepatology 28, 211–218.
    [Google Scholar]
  6. Choo, Q. L., Richman, K. H., Han, J. H., Berger, K., Lee, C., Dong, C., Gallegos, C., Coit, D., Medina-Selby, R., Barr, P. J., Weiner, A. J., Bradley, D. W., Kuo, G. & Houghton, M. ( 1991; ). Genetic organization and diversity of the hepatitis C virus. Proc Natl Acad Sci U S A 88, 2451–2455.[CrossRef]
    [Google Scholar]
  7. Cook, E. B., Stahl, J. L., Lowe, L., Chen, R., Morgan, E., Wilson, J., Varro, R., Chan, A., Graziano, F. M. & Barney, N. P. ( 2001; ). Simultaneous measurement of six cytokines in a single sample of human tears using microparticle-based flow cytometry: allergics vs. non-allergics. J Immunol Methods 254, 109–118.[CrossRef]
    [Google Scholar]
  8. Daar, E. S., Lynn, H., Donfield, S., Gomperts, E., O'Brien, S. J., Hilgartner, M. W., Hoots, W. K., Chernoff, D., Arkin, S., Wong, W. Y. & Winkler, C. A. ( 2001; ). Hepatitis C virus load is associated with human immunodeficiency virus type 1 disease progression in hemophiliacs. J Infect Dis 183, 589–595.[CrossRef]
    [Google Scholar]
  9. Greub, G., Ledergerber, B., Battegay, M., Grob, P., Perrin, L., Furrer, H., Burgisser, P., Erb, P., Boggian, K., Piffaretti, J. C., Hirschel, B., Janin, P., Francioli, P., Flepp, M. & Telenti, A. ( 2000; ). Clinical progression, survival, and immune recovery during antiretroviral therapy in patients with HIV-1 and hepatitis C virus coinfection: the Swiss HIV Cohort Study. Lancet 356, 1800–1805.[CrossRef]
    [Google Scholar]
  10. Herbein, G. & O'Brien, W. A. ( 2000; ). Tumor necrosis factor (TNF)-alpha and TNF receptors in viral pathogenesis. Proc Soc Exp Biol Med 223, 241–257.[CrossRef]
    [Google Scholar]
  11. Hilfenhaus, J., Groner, A., Nowak, T. & Weimer, T. ( 1997; ). Analysis of human plasma products: polymerase chain reaction does not discriminate between live and inactivated viruses. Transfusion 37, 935–940.[CrossRef]
    [Google Scholar]
  12. Kanto, T., Hayashi, N., Takehara, T., Tatsumi, T., Kuzushita, N., Ito, A., Sasaki, Y., Kasahara, A. & Hori, M. ( 1999; ). Impaired allostimulatory capacity of peripheral blood dendritic cells recovered from hepatitis C virus-infected individuals. J Immunol 162, 5584–5591.
    [Google Scholar]
  13. Khabar, K. S., Al-Zoghaibi, F., Al-Ahdal, M. N., Murayama, T., Dhalla, M., Mukaida, N., Taha, M., Al-Sedairy, S. T., Siddiqui, Y., Kessie, G. & Matsushima, K. ( 1997; ). The alpha chemokine, interleukin 8, inhibits the antiviral action of interferon alpha. J Exp Med 186, 1077–1085.[CrossRef]
    [Google Scholar]
  14. Lane, B. R., Lore, K., Bock, P. J., Andersson, J., Coffey, M. J., Strieter, R. M. & Markovitz, D. M. ( 2001; ). Interleukin-8 stimulates human immunodeficiency virus type 1 replication and is a potential new target for antiretroviral therapy. J Virol 75, 8195–8202.[CrossRef]
    [Google Scholar]
  15. Lanford, R. E., Sureau, C., Jacob, J. R., White, R. & Fuerst, T. R. ( 1994; ). Demonstration of in vitro infection of chimpanzee hepatocytes with hepatitis C virus using strand-specific RT/PCR. Virology 202, 606–614.[CrossRef]
    [Google Scholar]
  16. Laskus, T., Radkowski, M., Wang, L. F., Vargas, H. & Rakela, J. ( 1997; ). Lack of evidence for hepatitis G virus replication in the livers of patients coinfected with hepatitis C and G viruses. J Virol 71, 7804–7806.
    [Google Scholar]
  17. Laskus, T., Radkowski, M., Wang, L. F., Jang, S. J., Vargas, H. & Rakela, J. ( 1998; ). Hepatitis C virus quasispecies in patients infected with HIV-1: correlation with extrahepatic viral replication. Virology 248, 164–171.[CrossRef]
    [Google Scholar]
  18. Laskus, T., Radkowski, M., Piasek, A., Nowicki, M., Horban, A., Cianciara, J. & Rakela, J. ( 2000a; ). 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]
  19. Laskus, T., Radkowski, M., Wang, L. F., Nowicki, M. & Rakela, J. ( 2000b; ). Uneven distribution of hepatitis C virus quasispecies in tissues from subjects with end-stage liver disease: confounding effect of viral adsorption and mounting evidence for the presence of low-level extrahepatic replication. J Virol 74, 1014–1017.[CrossRef]
    [Google Scholar]
  20. Laskus, T., Wang, L. F., Radkowski, M., Vargas, H., Nowicki, M., Wilkinson, J. & Rakela, J. ( 2001; ). Exposure of hepatitis C virus (HCV) RNA-positive recipients to HCV RNA-positive blood donors results in rapid predominance of a single donor strain and exclusion and/or suppression of the recipient strain. J Virol 75, 2059–2066.[CrossRef]
    [Google Scholar]
  21. Lehmann, C., Sprenger, H., Nain, M., Bacher, M. & Gemsa, D. ( 1996; ). Infection of macrophages by influenza A virus: characteristics of tumour necrosis factor-alpha (TNF alpha) gene expression. Res Virol 147, 123–130.[CrossRef]
    [Google Scholar]
  22. Lerat, H., Rumin, S., Habersetzer, F., Berby, F., Trabaud, M. A., Trepo, 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]
  23. Mahe, Y., Mukaida, N., Kuno, K., Akiyama, M., Ikeda, N., Matsushima, K. & Murakami, S. ( 1991; ). Hepatitis B virus X protein transactivates human interleukin-8 gene through acting on nuclear factor κB and CCAAT/enhancer-binding protein-like cis-elements. J Biol Chem 266, 13759–13763.
    [Google Scholar]
  24. Mogensen, S. C. ( 1979; ). Role of macrophages in natural resistance to virus infections. Microbiol Rev 43, 1–26.
    [Google Scholar]
  25. Mori, N., Mukaida, N., Ballard, D. W., Matsushima, K. & Yamamoto, N. ( 1998; ). Human T-cell leukemia virus type I Tax transactivates human interleukin 8 gene through acting concurrently on AP-1 and nuclear factor-kappa B-like sites. Cancer Res 58, 3993–4000.
    [Google Scholar]
  26. Mukaida, N. ( 2000; ). Interleukin-8: an expanding universe beyond neutrophil chemotaxis and activation. Int J Hematol 72, 391–398.
    [Google Scholar]
  27. Murayama, T., Kuno, K., Jisaki, F., Obuchi, M., Sakamuro, D., Furukawa, T., Mukaida, N. & Matsushima, K. ( 1994; ). Enhancement human cytomegalovirus replication in a human lung fibroblast cell line by interleukin-8. J Virol 68, 7582–7585.
    [Google Scholar]
  28. Murayama, T., Ohara, Y., Obuchi, M., Khabar, K. S., Higashi, H., Mukaida, N. & Matsushima, K. ( 1997; ). Human cytomegalovirus induces interleukin-8 production by a human monocytic cell line, THP-1, through acting concurrently on AP-1- and NF-κB-binding sites of the interleukin-8 gene. J Virol 71, 5692–5695.
    [Google Scholar]
  29. Nakajima, N., Hijikata, M., Yoshikura, H. & Shimizu, Y. K. ( 1996; ). Characterization of long-term cultures of hepatitis C virus. J Virol 70, 3325–3329.
    [Google Scholar]
  30. Navas, S., Martin, J., Quiroga, J. A., Castillo, I. & Carreno, V. ( 1998; ). Genetic diversity and tissue compartmentalization of the hepatitis C virus genome in blood mononuclear cells, liver, and serum from chronic hepatitis C patients. J Virol 72, 1640–1646.
    [Google Scholar]
  31. Nowak, T., Niedrig, M., Bernhardt, D. & Hilfenhaus, J. ( 1993; ). Inactivation of HIV, HBV, HCV related viruses and other viruses in human plasma derivatives by pasteurisation. Dev Biol Stand 81, 169–176.
    [Google Scholar]
  32. Oliver, K. G., Kettman, J. R. & Fulton, R. J. ( 1998; ). Multiplexed analysis of human cytokines by use of the FlowMetrix system. Clin Chem 44, 2057–2060.
    [Google Scholar]
  33. Polyak, S. J., Khabar, K. S., Paschal, D. M., Ezelle, H. J., Duverlie, G., Barber, G. N., Levy, D. E., Mukaida, N. & Gretch, D. R. ( 2001a; ). Hepatitis C virus nonstructural 5A protein induces interleukin-8, leading to partial inhibition of the interferon-induced antiviral response. J Virol 75, 6095–6106.[CrossRef]
    [Google Scholar]
  34. Polyak, S. J., Khabar, K. S., Rezeiq, M. & Gretch, D. R. ( 2001b; ). Elevated levels of interleukin-8 in serum are associated with hepatitis C virus infection and resistance to interferon therapy. J Virol 75, 6209–6211.[CrossRef]
    [Google Scholar]
  35. Sansonno, D., Iacobelli, A. R., Cornacchiulo, V., Iodice, G. & Dammacco, F. ( 1996; ). Detection of hepatitis C virus (HCV) proteins by immunofluorescence and HCV RNA genomic sequences by non-isotopic in situ hybridization in bone marrow and peripheral blood mononuclear cells of chronically HCV-infected patients. Clin Exp Immunol 103, 414–421.
    [Google Scholar]
  36. Shimizu, Y. K., Purcell, R. H. & Yoshikura, H. ( 1993; ). Correlation between the infectivity of hepatitis C virus in vivo and its infectivity in vitro. Proc Natl Acad Sci U S A 90, 6037–6041.[CrossRef]
    [Google Scholar]
  37. Shimizu, Y. K., Igarashi, H., Kanematu, T., Fujiwara, K., Wong, D. C., Purcell, R. H. & Yoshikura, H. ( 1997; ). Sequence analysis of the hepatitis C virus genome recovered from serum, liver, and peripheral blood mononuclear cells of infected chimpanzees. J Virol 71, 5769–5773.
    [Google Scholar]
  38. Simmonds, P., Holmes, E. C., Cha, T. A., Chan, S. W., McOmish, F., Irvine, B., Beall, E., Yap, P. L., Kolberg, J. & Urdea, M. S. ( 1993; ). Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region. J Gen Virol 74, 2391–2399.[CrossRef]
    [Google Scholar]
  39. Thomas, D. L., Rich, J. D., Schuman, P., Smith, D. K., Astemborski, J. A., Nolt, K. R. & Klein, R. S. ( 2001; ). Multicenter evaluation of hepatitis C RNA levels among female injection drug users. J Infect Dis 183, 973–976.[CrossRef]
    [Google Scholar]
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