Immunopathogenesis of dengue virus infection

Dengue virus infection causes dengue fever (DF), dengue hemorrhagic fever ( DHF), and dengue shock syndrome (DSS), whose pathogeneses are not clearly u nderstood. Current hypotheses of antibody-dependent enhancement, virus viru lence, and IFN-gamma /TNF alpha -mediated immunopathogenesis are insufficie nt to explain clinical manifestations of DHF/DSS such as thrombocytopenia a nd hemoconcentration. Dengue virus infection induces transient immune aberr ant activation of CD4/CD8 ratio inversion and cytokine overproduction, and infection of endothelial cells and hepatocytes causes apoptosis and dysfunc tion of these cells. The coagulation and fibrinolysis systems are also acti vated after dengue virus infection. We propose a new hypothesis for the imm unopathogenesis for dengue virus infection. The aberrant immune responses n ot only impair the immune response to clear the virus, but also result in o verproduction of cytokines that affect monocytes, endothelial cells, and he patocytes. Platelets are destroyed by crossreactive anti-platelet autoantib odies. Dengue-virus-induced vasculopathy and coagulopathy must be involved in the pathogenesis of hemorrhage, and the unbalance between coagulation an d fibrinolysis activation increases the likelihood of severe hemorrhage in DHF/DSS. Hemostasis is maintained unless the dysregulation of coagulation a nd fibrinolysis persists. The overproduced IL-6 might play a crucial role i n the enhanced production of anti-platelet or anti-endothelial cell autoant ibodies, elevated levels of tPA, as well as a deficiency in coagulation. Ca pillary leakage is triggered by the dengue virus itself or by antibodies to its antigens. This immunopathogenesis of DHF/DSS can account for specific characteristics of clinical, pathologic, and epidemiological observations i n dengue virus infection. Copyright (C) 2001 National Science Council, ROC and S. Karger AG, Basel.