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

Abstract

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.