Searching for the dengue virus Achilles heel

Abstract

Dengue viruses are a major public health problem throughout the tropical world, with up to 100 million people infected annually. Infection can result in acute febrile illness (dengue fever) and in severe cases is associated with abnormalities in vascular permeability and haemostasis (dengue haemorrhagic fever) that can lead to sudden and fatal hypovolemic shock (dengue shock syndrome). The incidence of dengue has steadily increased over the last two to three decades such that it is now endemic throughout much of the tropics and is the leading cause of infant mortality in some South-East Asian countries. Australia has not escaped this territorial expansion of dengue, with regular epidemic outbreaks now occurring in North Queensland. The epidemic that lasted for most of the summer of 2008–2009 involved the circulation of all four dengue virus serotypes and more than 1,000 confirmed cases. Coupled with the potential impact that climate change may have in increasing the range of its mosquito vector, there is growing concern that dengue may become endemic in Australia. Considerable challenges have accompanied the development of vaccine strategies for dengue and this has reinforced the importance of the complementary development of antiviral therapies. Part of our dengue research efforts has been focused on identifying viral targets for inhibitor design.