The dengue virus is the causative agent of a wide spectrum of clinical manifestations, ranging from mild acute febrile illness to classical dengue fever, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). DHF and DSS are the potentially fatal forms of dengue virus infection, which has become an intractable public health problem in many countries. The pathogeneses of DHF/ DSS are not clearly understood. One hypothesis concerning virus virulence and the immune enhancement hypothesis has been debated. Although dengue disease severity has been associated with evidence of genetic differences in dengue strains, virus virulence has been difficult to measure because of the lack of in vivo and in vitro models of the disease.