Enterovirus 71 Infection of Human Immune Cells Induces the Production of Proinflammatory Cytokines

A proinflammatory cytokine storm has been proposed to explain the pathogenesis of enterovirus 71 (EV71)-induced fatalities; however, the mechanism to induce these cytokines during EV71 infection remains unclear. Since most of the proinflammatory cytokines are produced by immune cells, we tested whether EV71 infects human immune cells and induces cytokine production. EV71 infection of a human T cell line (Jurkat), macrophage cell line (THP-1), and freshly isolated human peripheral blood mononuclear cells was demonstrated using RT-PCR and immunofluorescence assays in vitro. In addition, live but not UV-inactivated EV71 increased the secretion of two proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and macrophage migration inhibitory factor (MIF) by immune cells, which was inhibited in the presence of actinomycin D. RT-PCR further confirmed that EV71 infection of immune cells triggered the de novo synthesis of MIF mRNA. Therefore, our results suggest that the production of TNF-α and MIF induced by EV71 infection of immune cells may contribute to the proinflammatory cytokine storm during EV71 infection.