A genomics comparison of affected individuals as a novel approach to investigating pathogenesis of severe disease caused by dengue virus infection

Of the millions of humans infected with the dengue virus worldwide each year a relatively small proportion develop the most severe manifestations of disease, either dengue haemorrhagic fever (DHF) or dengue shock syndrome (DSS). Nonetheless, as a consequence countless people are debilitated and the global death toll continues to rise annually. By comparing the genomes of individuals who have suffered DHF/DSS with those who have experienced only the more common milder form of disease, dengue fever, differences in genetic predisposition to infection may be revealed. This may be beneficial in two ways. First, if mutations are identified in protein-coding genes, the expressed proteins may be investigated for their putative role in DHS/DSS pathogenesis. This could provide novel targets for anti-viral drug design specifically against DHF/DSS. Second, if several reliable genetic markers were to be uncovered, this would facilitate the rapid identification of patients who are at high risk of suffering DHF/DSS. The routine use in a hospital setting of such a protocol to determine genetic susceptibility could lighten the burden of disease on public health care systems in dengue-endemic regions.