Dengue virus: epidemiology, biology, and disease aetiology

Dengue is a vector-borne viral disease caused by the flavivirus dengue virus (DENV). Approximately 400 million cases and 22 000 deaths occur due to dengue worldwide each year. It has been reported in more than 100 countries in tropical and subtropical regions. A positive-stranded enveloped RNA virus (DENV) is principally transmitted by Aedes mosquitoes. It has four antigenically distinct serotypes, DENV-1 to DENV-4, with different genotypes and three structural proteins and seven non-structural proteins. Clinical symptoms of dengue range from mild fever to severe dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), with thrombocytopenia, leucopenia, and increased vascular permeability. Although primary infection causes activation of immune responses against DENV serotypes, the severity of the disease is enhanced via heterotypic infection by various serotypes as well as antibody-dependent enhancement (ADE). The first licensed DENV vaccine was tetravalent CYD Denvaxia, but it has not been approved in all countries. The lack of a suitable animal model, a proper mechanistic study in pathogenesis, and ADE are the main hindrances in vaccine development. This review summarizes the current knowledge on DENV epidemiology, biology, and disease aetiology in the context of prevention and protection from dengue virus disease.