Abstract
Dengue virus (DENV) is a mosquito-borne flavivirus that causes serious human disease and mortality worldwide. There is no specific antiviral therapy or vaccine for DENV infection. Alterations in gene expression during DENV infection of the mosquito and the impact of these changes on virus infection are important events to investigate in hopes of creating new treatments and vaccines. We previously identified 203 genes that were ≥5-fold differentially upregulated during flavivirus infection of the mosquito. Here, we examined the impact of silencing 100 of the most highly upregulated gene targets on DENV infection in its mosquito vector. We identified 20 genes that reduced DENV infection by at least 60% when silenced. We focused on one gene, a putative cysteine rich venom protein (SeqID AAEL000379; CRVP379), whose silencing significantly reduced DENV infection in Aedes aegypti cells. Here, we examine the requirement for CRVP379 during DENV infection of the mosquito and investigate the mechanisms surrounding this phenomenon. We also show that blocking CRVP379 protein with either RNAi or specific antisera inhibits DENV infection in Aedes aegypti. This work identifies a novel mosquito gene target for controlling DENV infection in mosquitoes that may also be used to develop broad preventative and therapeutic measures for multiple flaviviruses.
Highlights
Dengue virus (DENV) is the most important arbovirus in tropical areas leading to substantial pediatric morbidity and mortality worldwide [1,2,3,4,5,6]
We look at a mosquito protein, CRVP379, whose gene expression was highly increased during DENV infection in mosquitoes
We show a requirement for CRVP379 during DENV infection in the mosquito and a correlation between the levels of CRVP379 and levels of infection
Summary
Dengue virus (DENV) is the most important arbovirus in tropical areas leading to substantial pediatric morbidity and mortality worldwide [1,2,3,4,5,6]. DENV is transmitted to humans via the bite of an infected mosquito of the Aedes spp. Infection with DENV in humans can result in dengue fever (DF), dengue shock symptom (DSS) and dengue hemorrhagic fever (DHF), the latter two that can lead to severe disease and death. The increase in number of cases despite vector control indicates that these strategies are not as effective as expected, and that new tools need be developed to alleviate disease burden in endemic areas [12,13,14]
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