Dengue Virus Host Factors

Abstract

Dengue fever and dengue hemorrhagic fever are estimated to afflict 50-100 million people annually and are caused by one of the four serotypes of dengue virus. Dengue virus is carried and transmitted to humans by mosquitoes of the Aedes genus. Given the broad geographic distribution of Aedes mosquitoes, it has been estimated that nearly half the world's population is at risk of contracting the disease. Currently, no vaccine or specific antiviral treatment is available to combat this emerging menace. A greater understanding of how dengue virus interacts with its insect and human hosts will facilitate the intelligent design of specific antivirals to combat the disease and enable the selective breeding of mosquitoes resistant to the virus. Although the genomes of the two primary mosquito vectors have been sequenced, the molecular tools necessary for conducting a systematic genetic analysis of host factors required for DEN infection are not yet available. These tools do however exist in the closely related fruit fly, Drosophila melanogaster. By using a strain of dengue virus that was adapted to propagate in fruit fly cells, we completed a full genetic screen for host factors required for efficient dengue virus propagation. When homologues of these host factors were assayed in a human cell line, over half were also shown to be required for efficient viral propagation. This indicates that while the virus is utilizing many of the same pathways in both of its hosts, the interaction with the insect vector has unique features that may contribute to the observed lack of pathogenesis in mosquitoes.