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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
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: 463–466
Boonpucknavig V, Bhamarapravati N, Boonpucknavig S, Futrakul P, Tanpaichitr P (1976) Glomerular changes in dengue haemorrhagic fever. Arch Pathol Lab Med 100: 206–212
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: 5086–5091
Clark SC, Kamen R (1987) The human hematopoietic colony stimulating factors. Science 236: 1229–1236
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: 7629–7633
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: 506–508
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: 625–632
Halstead SB (1980) Immunological parameters of togavirus disease syndrome. In: Schlesinger RW (ed) The togaviruses: biology, structure, replication. Academic Press, New York, pp 107–173
Halstead SB (1981) Dengue haemorrhagic fever—a public health problem and field for research. Bull WHO 58: 1–21
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: 218–229
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: 830–836
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: 73–76
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 93–131
Kaushansky K, Lin N, Adamson JW (1988) Interleukin 1 stimulates fibroblasts to synthesize granulocyte-macrophage and granulocyte colony stimulating factors. J Clin Invest 81: 92–97
Kurane I, Ennis FA (1987) Induction of interferon α from human lymphocytes by autologous, dengue virus-infected monocytes. J Exp Med 166: 999–1010
Kurane I, Ennis FA (1988) Production of interferon alpha by dengue virus-infected human monocytes. J Gen Virol 69: 445–459
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: 223–230
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 763–814
Oppenheim JJ, Kovacs EJ, Matsushima K, Durum SK (1986) There is more than one interleukin 1. Immunol Today 7: 45–56
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: 508–512
Wong GG, Clark SC (1988) Multiple actions of interleukin 6 within a cytokine network. Immunol Today 9: 137–139
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: 2529–2537
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kurane, I., Janus, J. & Ennis, F.A. Dengue virus infection of human skin fibroblasts in vitro production of IFN-β, IL-6 and GM-CSF. Archives of Virology 124, 21–30 (1992). https://doi.org/10.1007/BF01314622
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01314622