title: The pathogenesis of dengue.
abstract: OBJECTIVE
  Dengue is one of the most rapidly spreading vector-borne diseases in the world, with the incidence increasing 30-fold in the past 50 years. There are currently no licensed treatments or vaccines for dengue. This review covers the recent advances in our understanding of dengue pathogenesis, including host and viral determinants.
  
  
  RESULTS
  The pathogenesis of severe dengue is thought to be immune-mediated due to the timing of the clinical manifestations and higher incidence in secondary infections with a heterologous serotype. Recent evidence has provided further information of neutralizing versus enhancing monoclonal antibodies and their target epitopes on the dengue virion, which has major implications for vaccine design. The role of T-cell immunopathology has also been advanced with recent evidence of cross-reactive high pro-inflammatory cytokine producing T cells predominating in severe dengue. Recent large genome-wide association studies have identified specific susceptibility loci associated with severe disease. Epidemiological studies have served to define certain at-risk groups and specific viral virulence factors have recently been described.
  
  
  CONCLUSIONS
  The pathogenesis of dengue is likely to be a complex interplay of host immunity and genetic predisposition combined with certain viral virulence factors. Better understanding of the underlying mechanisms leading to severe dengue is crucial if we are to develop prognostic markers, novel diagnostics and therapeutics and ultimately a balanced and safe vaccine.
authors: Department of Medicine, Imperial College, Hammersmith Campus, London, UK. s.yacoub@imperial.ac.uk
authors: Sophie
authors: S
authors: Yacoub
authors: Juthathip
authors: J
authors: Mongkolsapaya
authors: Gavin
authors: G
authors: Screaton
mesh_terms: D003715:Dengue / Q000235:genetics / Q000276:immunology; D003716:Dengue Virus / Q000235:genetics / Q000472:pathogenicity*; D020022:Genetic Predisposition to Disease; D006790:Host-Parasite Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D056724:Immunity, Humoral / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D037521:Virulence Factors
chemical_list: D037521:Virulence Factors