APOPTOTIC CELL-DEATH IN RESPONSE TO DENGUE VIRUS-INFECTION - THE PATHOGENESIS OF DENGUE HEMORRHAGIC-FEVER REVISITED

Background: Dengue virus infection may be asymptomatic or lead to undi fferentiated febrile illness or dengue haemorrhagic fever and dengue s hock syndrome (DHF/DSS). The major clinical manifestations of DHF/DSS are high fever, haemorrhage, hepatomegaly and circulatory failure. Obj ectives: The relatively high level of viraemia only a few days after i nfection may reflect a large number of replication sites. However, the degree of cell injury in fatal cases of DHF/DSS is not sufficient to explain death and suggests metabolic disturbance rather than tissue de struction. This theory was investigated in this study. Results: We dem onstrated that replication of dengue virus in infected cells induces s tress leading to apoptotic cell death in vitro and in vivo. Conclusion s: The elimination of apoptotic bodies by phagocytic cells is a previo usly unsuspected pathway of dengue virus clearance from infected tissu es. However, the mechanisms of host defence involving apoptosis and ph agocytic cell activation may cause local tissue injury or transient ho meostasis imbalance and may trigger further deleterious events. (C) 19 98 Elsevier Science B.V. All rights reserved.