A Research Blog

Dengue fever, caused by the dengue virus, is a tropical disease transmitted by mosquitoes that threatens more than one third of the worldwide population, making it one of the most important arboviruses in the world. They have important economic consequences because of the burden to hospitals, work absenteeism and risk of death for severe symptomatic cases.

Dengue viruses are primarily transmitted from human-to-human by Aedes aegypti mosquitoes. While the mechanisms leading to dengue infection in humans have been defined, there is a lack of knowledge on how dengue viruses influence mosquito transmission and infection, or the genetic factors that affect virus replication in mosquitoes.

With this quest in mind, researchers at Duke-NUS Medical School’s Emerging Infectious Disease Programme led by Assistant Professor Julien Pompon and Professor Mariano A Garcia-Blanco set out to identify the viral determinants of transmission, as well as the mechanism by which dengue viruses harness evolution to cycle between the two hosts.

To understand this better, the team carried out tests on infected Aedes aegypti mosquitoes, combining oral infection and reverse genetics. The researchers reported that epidemic isolates produced more subgenomic flaviviral RNA (sfRNA) and infectious particles in salivary glands, thereby enhancing infectivity of the saliva. They identified two substitutions in the virus untranslated region (3’ UTR), from which the sfRNA is generated, as responsible for these phenotypes. Furthermore, they determined that increased saliva infectivity was caused by sfRNA disruption of the immune response in salivary glands.

This Duke-NUS study, published in PLOS Pathogens, identified viral determinants of increased transmission associated with high epidemiological fitness, and in doing so revealed how the virus disrupts mosquito immunity to trigger epidemics. Together with previous works that demonstrate the influence of sfRNA on dengue infectivity in human, this study supports the model that sfRNA evolution is constrained in both mosquito and human hosts.

The study should help Singapore and tropical nations better control dengue epidemics, as the identification and characterization of viral determinants of mosquito transmission will help forecast the emergence of dengue virus strains with higher epidemic potential. 

Photo: Shih-Chia Yeh and Geraldine Tibayrenc

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