Abstract
BackgroundDengue fever is the most rapidly spreading mosquito-borne viral disease globally. More than 2.5 billion people live in dengue-endemic areas. Previous studies suggested an interrelationship between diabetes mellitus (DM) and dengue hemorrhagic fever (DHF). Conversely, glycolysis is a critical metabolic pathway for optimal dengue virus (DENV) replication. However, little is known concerning the effect of glucose on DENV replication in mosquitoes. In this study, we investigated the impact of glucose on DENV replication in mosquitoes Aedes aegypti.MethodsMosquitoes (Ae. aegypti UGAL/Rockefeller strain) were orally infected with DENV (serotype 2, 16681 strain) through infectious blood feeding. The DENV infection and transmission rates were determined by examining mosquito bodies and saliva, respectively, for DENV positivity at different time points after infection. In addition, a reverse genetic approach was applied by introducing double-stranded RNA against genes of interest into the mosquitoes to inhibit gene expression.ResultsOur data revealed a significant increase of DENV genome levels in mosquitoes consuming an infectious blood meal supplemented with glucose, suggesting that blood glucose is an important factor for viral replication. Interestingly, a significant increase of DENV E protein levels was detected in the saliva 4 days faster in mosquitoes that consumed infectious blood meals supplemented with glucose than in those consuming infectious blood meals alone. Furthermore, we perform RNAi to silence AKT or TOR and investigate the molecular mechanism regulating the glucose-mediated enhancement of viral replication. Silencing of AKT or TOR significantly reduced DENV titers in mosquitoes.ConclusionsThis study suggested that blood glucose is beneficial to DENV replication and that it facilitates virus transmission in mosquitoes via AKT and TOR signaling. Therefore, our results strengthen our understanding of dengue fever and DM co-morbidity and possibly reveal new targets for specific antiviral therapies.Graphical abstract
Highlights
Dengue fever is the most rapidly spreading mosquito-borne viral disease globally
We investigated the possibility that blood glucose promotes dengue virus (DENV) replication and facilitates viral transmission in mosquitoes via AKT and TOR signaling
Our data revealed a significant increase of DENV genome levels in mosquitoes consuming an infectious blood meal supplemented with glucose, suggesting the importance of blood glucose for viral replication
Summary
Dengue fever is the most rapidly spreading mosquito-borne viral disease globally. Several important and widespread infectious diseases, such as malaria, dengue fever, and Zika, are transmitted primarily by mosquitoes. These diseases kill more than 1 million people annually, and more than 2 billion people are at risk worldwide [1]. Dengue fever is one of the most common arthropodborne viral diseases globally, and it is caused by four dengue virus (DENV) serotypes (DENV1–4). DENV is a positive-stranded RNA virus belonging to the Flaviviridae family that is transmitted to humans primarily through the bite of infected Aedes mosquitoes. DENV infection causes several disease manifestations, ranging from undifferentiated fever and dengue fever to life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) [1, 3, 4]
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