Abstract
Mosquitoes act as vectors of numerous pathogens that cause human diseases. Dengue virus (DENV) transmitted by mosquito, Aedes aegypti, is responsible for dengue fever epidemics worldwide with a serious impact on human health. Currently, disease control mainly relies on vector targeted intervention strategies. Therefore, it is imperative to understand the molecular mechanisms underlying the innate immune response of mosquitoes against pathogens. In the present study, the expression profiles of immunity-related genes in the midgut responding to DENV infection by feeding were analyzed by transcriptome and quantitative real-time PCR. The level of Antimicrobial peptides (AMPs) increased seven days post-infection (d.p.i.), which could be induced by the Toll immune pathway. The expression of reactive oxygen species (ROS) genes, including antioxidant genes, such as HPX7, HPX8A, HPX8B, HPX8C were induced at one d.p.i. and peaked again at ten d.p.i. in the midgut. Interestingly, down-regulation of the antioxidant gene HPX8C by RNA interference led to reduction in the virus titer in the mosquito, probably due to the elevated levels of ROS. Application of a ROS inhibitor and scavenger molecules further established the role of oxygen free radicals in the modulation of the immune response to DENV infection. Overall, our comparative transcriptome analyses provide valuable information about the regulation of immunity related genes in the transmission vector in response to DENV infection. It further allows us to identify novel molecular mechanisms underlying the host-virus interaction, which might aid in the development of novel strategies to control mosquito-borne diseases.
Highlights
Hematophagous vectors such as mosquitoes transmit a variety of harmful infections that cause devastating diseases, such as malaria, dengue fever, and Zika syndrome [1]
In order to identify the genes activated in response to viral infection, we performed global transcriptome profiling in Ae. aegypti mosquitoes after blood feeding
We observed that the Dengue virus (DENV) level increased significantly in both the midgut and carcass when fed with a blood meal containing a viral titer of 106 Pfu/ml (S1A and S1B Fig)
Summary
Hematophagous vectors such as mosquitoes transmit a variety of harmful infections that cause devastating diseases, such as malaria, dengue fever, and Zika syndrome [1]. Mosquitoes, like other insects, do not possess adaptive immunity like that of vertebrates [3]; the innate immune system is essential for controlling parasite and arbovirus infections [4,5,6,7]. Much knowledge has already been acquired from research on anti-Plasmodium and antibacterial defenses of mosquitoes. In the mosquito fat body, Toll and IMD are two major immune signaling pathways. Activation of the Toll and IMD pathways allows NF-κB factors to enter the nucleus and transcriptionally activate the expression of Antimicrobial peptides (AMPs) and other immunity related genes [8]. It has been reported that transgenic mosquitoes co-expressing two or more effector molecules, such as Cecropin A or Defensin A, with synergistic effects on parasites exhibit anti-malarial phenotypes [10]. The JAK-STAT pathway has been shown to be involved in anti-Plasmodium defense [11]
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