PATHOGENESIS OF DENGUE VIRAL DISEASES

In recent efficacy trials of a dengue vaccine candidate, about 7-15% of volunteers in the control group manifested at least one of the three dengue hemorrhagic fever (DHF)-defining abnormalities (hemorrhage, thrombocytopenia, and plasma leakage) during symptomatic dengue virus infection. A high risk of developing DHF observed in secondarily infected persons is related to an increased viral burden. Complex interactions between structurally heterogeneous viral particles and pre-existing antibodies specific for the viral envelope glycoproteins, E and prM, are thought to play a role in enhancing virus replication. Concomitant high level of circulating NS1, a virally encoded glycoprotein that is essential for viral RNA replication, may cause plasma leakage through its direct and indirect effects on the vascular endothelial cells. Cross-reaction of anti-NS1 antibodies generated during dengue virus infection with platelets may lead to thrombocytopenia. Dengue serotype cross-reactive T cells rapidly expand during the secondary infection, and their levels in the circulation are associated with the development of DHF. However, the role of T cells in mediating an increase in vascular permeability at the tissue level remains unclear.