Dengue Virus: Host-Pathogen Interactions and Emerging Role of DNA Vaccines

Abstract

Dengue virus infections are a major cause of mortality and morbidity in Southeast Asia, South and Central America with 24'000 deaths annually. Two factors are accountable for the severe outcomes of Dengue Hemorrhagic Fever (DHF); one is the virulence of the virus and second is the cross-reactivity of various dengue serotypes with the immune system of the host. Rapid rise in the levels of various cytokines, particularly Tumor Necrosis Factor-alpha (TNF-α), Interleukin-2 (IL-2), Interleukin-6 (IL-6), Interleukin-8 (IL-8) have a major role in inducing distinctive clinical presentations of DHF. These range from simple plasma leakage to hemorrhagic problems and even shock. Another hallmark of DHF is the presence of cross reactive primary antibodies which produce an intense immune response in secondary infection resulting in immune mediated pathology seen in DHF. There have been many attempts made in the past for the development of a suitable vaccine for dengue fever. Vaccination using plasmid DNA against dengue fever is an active area of research. In this review the role of different cells in the multiplication of dengue virus and viral interactions with the immune system have been discussed. Special emphasis is given to the nature of DNA vaccines in general developmental efforts of a dengue fever vaccine.