Archives of Virology

, Volume 124, Issue 1–2, pp 21–30 | Cite as

Dengue virus infection of human skin fibroblasts in vitro production of IFN-β, IL-6 and GM-CSF

  • I. Kurane
  • J. Janus
  • F. A. Ennis
Original Papers

Summary

Dengue virus is transmitted to humans by the bite of infected mosquitos. In our efforts to understand the pathogenesis of dengue virus infection, we examined whether skin fibroblasts can be infected in vitro with dengue viruses. Fibroblasts could be infected with dengue viruses, yellow fever virus and West Nile virus. Dengue virus antigen-positive cells were detected as early as 4h and the percentage of dengue virus antigen-positive cells reached maximum levels by 24h after infection. High titers of infectious dengue virus were also detected in the culture supernatants at 20h after infection. Dengue virus-infected fibroblasts produced interferon-β (IFN-β), and the IFN-β protected uninfected fibroblasts from dengue virus infection. Dengue virus-infected fibroblasts also produced interleukin 6 (IL-6) and granulocyte macrophage colony stimulation factor (GM-CSF).

These results suggest that skin fibroblasts may be one of the cell types which first support dengue virus and other flavivirus infections in vivo after introduction by the bite of infected mosquito, and that production of IFN-β, IL-6, and GM-CSF by these virus-infected fibroblasts may be important host immune responses to control flavivirus infections.

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References

  1. 1.
    Boonpucknavig S, Boonpucknavig V, Hamarapravati BN, Nimmannitya S (1979) Immunofluorencence study of skin rash in patients with dengue haemorrhagic fever. Arch Pathol Lab Med 103: 463–466Google Scholar
  2. 2.
    Boonpucknavig V, Bhamarapravati N, Boonpucknavig S, Futrakul P, Tanpaichitr P (1976) Glomerular changes in dengue haemorrhagic fever. Arch Pathol Lab Med 100: 206–212Google Scholar
  3. 3.
    Bukowski JF, Kurane I, Lai C-J, Bray M, Falgout B, Ennis FA (1989) Dengue virus-specific cross-reactive CD8+ human cytotoxic T lymphocytes. J Virol 63: 5086–5091Google Scholar
  4. 4.
    Clark SC, Kamen R (1987) The human hematopoietic colony stimulating factors. Science 236: 1229–1236Google Scholar
  5. 5.
    Garman RD, Jacobs KA, Clark SC, Raulet DH (1987) B-cell-stimulating factor 2 (β 2 interferon) functions as a second signal for interleukin 2 production by mature murine T cells. Proc Natl Acad Sci USA 82: 7629–7633Google Scholar
  6. 6.
    Grabstein KH, Urdal DL, Tushinski RJ, Mochizuki DY, Price VL, Cantrell MA, Gillis S, Conlon PJ (1986) Induction of macrophge tumericidal activity by granulocyte-macrophage colony stimulating factor. Science 232: 506–508Google Scholar
  7. 7.
    Haegeman G, Content J, Volckaert G, Derynck R, Tauernier J, Fiers W (1986) Structural analysis of the sequence coding for an inducible 26-kDa protein in human fibroblasts. Euro J Biochem 159: 625–632Google Scholar
  8. 8.
    Halstead SB (1980) Immunological parameters of togavirus disease syndrome. In: Schlesinger RW (ed) The togaviruses: biology, structure, replication. Academic Press, New York, pp 107–173Google Scholar
  9. 9.
    Halstead SB (1981) Dengue haemorrhagic fever—a public health problem and field for research. Bull WHO 58: 1–21Google Scholar
  10. 10.
    Halstead SB, O'Rourke EJ (1977) Dengue virus and mononuclear phagocytes. II. Identity of blood and tissue leukocytes supporting in vitro infection. J Exp Med 146: 218–229Google Scholar
  11. 11.
    Henchal EA, Gentry MK, McCown JM, Brandt WE (1982) Dengue virus-specific and flavivirus group determinants identified with monoclonal antibodies by indirect immunofluorescence. Am J Trop Med Hyg 314: 830–836Google Scholar
  12. 12.
    Hirano T, Yasukawa K, Harada H, Taga T, Watanabe Y, Matsuda T, Kashiwamura S, Nakajima K, Keyama K, Iwamatsu S, Tsunasawa S, Sakiyama F, Matsui H, Takahara Y, Taniguchi T, Kishimoto T (1986) Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature 324: 73–76Google Scholar
  13. 13.
    Holbrook KA, Wolff K (1987) The structure and development of skin. In: Fitzpatrick TB, Eilsen AZ, Wolff W, Freedbeerg IM, Austen KF (eds) Dermatology in general medicine. McGraw-Hill, New York, pp 93–131Google Scholar
  14. 14.
    Kaushansky K, Lin N, Adamson JW (1988) Interleukin 1 stimulates fibroblasts to synthesize granulocyte-macrophage and granulocyte colony stimulating factors. J Clin Invest 81: 92–97Google Scholar
  15. 15.
    Kurane I, Ennis FA (1987) Induction of interferon α from human lymphocytes by autologous, dengue virus-infected monocytes. J Exp Med 166: 999–1010Google Scholar
  16. 16.
    Kurane I, Ennis FA (1988) Production of interferon alpha by dengue virus-infected human monocytes. J Gen Virol 69: 445–459Google Scholar
  17. 17.
    Kurane I, Hebblewaite D, Ennis FA (1984) Lysis of dengue virus-infected cells by natural cell-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity. J Virol 52: 223–230Google Scholar
  18. 18.
    Monath TP (1990) Flaviviruses. In: Fields BN, Knipe DM, Chanock RN, Hirsch MS, Melnick JL, Monath TP, Roizman B, Shope B (eds) Virology. Raven Press, New York, pp 763–814Google Scholar
  19. 19.
    Oppenheim JJ, Kovacs EJ, Matsushima K, Durum SK (1986) There is more than one interleukin 1. Immunol Today 7: 45–56Google Scholar
  20. 20.
    Takei Y, Wong GG, Clark SC, Burakoff SJ, Herrmann SH (1988) B cell stimulatory factor-2 is involved in the differentiation of cytotoxic T lymphocytes. J Immunol 140: 508–512Google Scholar
  21. 21.
    Wong GG, Clark SC (1988) Multiple actions of interleukin 6 within a cytokine network. Immunol Today 9: 137–139Google Scholar
  22. 22.
    Zilberstein A, Ruggieri R, Korn JH, Revel M (1986) Structure and express of cDNA and genes for human interferon-beta-2, a distinct species inducible by growth stimulatory cytokines. EMBO J 5: 2529–2537Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • I. Kurane
    • 1
  • J. Janus
    • 1
  • F. A. Ennis
    • 1
  1. 1.Division of Infectious Diseases and Immunology, Department of MedicineUniversity of Massachusetts Medical CenterWorcesterUSA

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