T Cell Immunopathogenesis of Dengue Virus Infection

Dengue virus infections cause significant morbidity and mortality worldwide. Although initially believed to be an infection afflicting mainly the paediatric age group, this infection has been rapidly spreading across all age groups, with the first reports of the pandemic from South-East Asia dating back to the 1950s. Dengue virus belongs to the genus Flavivirus and has four serotypes, each of which may cause a spectrum of illness ranging from asymptomatic to mild febrile illness to severe and often fatal haemorrhagic disease. Despite our growing understanding of various facets of the infection, its pathogenesis still remains unclear, with the possibility of several mechanisms being involved simultaneously. The virus is taken up by dendritic cells, which, after antigen processing, presents it to T cells, leading to immune activation and release of a cascade of cytokines that are believed to mediate the systemic effects of plasma leakage and circulatory insufficiency. Thrombocytopenia develops due to the presence of cross-reacting antibodies to platelets and is responsible for the bleeding diathesis. The phenomenon of ‘original antigenic sin’ may explain the increased severity of illness during secondary infections, due to the presence of antibody to the previously infecting serotype. This leads to immune enhancement leading to the development of dengue shock syndrome (DSS). In addition, there is evidence for increased apoptosis and endothelial cell dysfunction, which may also contribute to its pathogenesis. Dengue virus infection in infants may cause increased morbidity due to the presence of pre-existing maternal antibodies in endemic areas. Several advances have been made in the treatment of acute infections, and recent preventive efforts have been directed towards the development of safe and effective vaccines against all the four serotypes in order to provide lasting protection from this dreaded infection, which still causes high morbidity and mortality in most developing countries.