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Aedes aegypti HPX8C modulates immune responses against viral infection

机译:埃及伊蚊HPX8C调节针对病毒感染的免疫反应

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摘要

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.
机译:蚊子是导致人类疾病的多种病原体的媒介。蚊子埃及伊蚊(Aedes aegypti)传播的登革热病毒(DENV)导致全球登革热流行,严重危害人类健康。当前,疾病控制主要依赖于靶向载体的干预策略。因此,必须了解潜在的蚊子针对病原体的免疫反应的分子机制。在本研究中,通过转录组和实时定量PCR分析了中性肠免疫应答相关基因在饲喂DENV感染中的表达情况。感染后7天(d.p.i.)抗菌肽(AMP)的水平增加,这可能是由Toll免疫途径诱导的。每天1 d。诱导活性氧(ROS)基因的表达,包括抗氧化剂基因,例如HPX7,HPX8A,HPX8B,HPX8C。在晚上10点再次达到顶峰在中肠。有趣的是,RNA干扰对抗氧化剂基因HPX8C的下调导致蚊子中的病毒滴度降低,这可能是由于ROS水平升高所致。 ROS抑制剂和清除剂分子的应用进一步确立了氧自由基在调节对DENV感染的免疫反应中的作用。总体而言,我们的比较转录组分析为响应DENV感染的传播载体中免疫相关基因的调控提供了有价值的信息。它进一步使我们能够确定宿主与病毒相互作用的潜在分子机制,这可能有助于控制蚊媒疾病的新策略的发展。

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