Exploring the effect of human blood microRNAs on mosquito biology

项目总结 小的非编码RNA，特别是microRNA，在调节各种不同的 生物过程及其失调会导致紊乱。最近，它们在细胞中的作用-细胞和 跨物种的交流也被揭示出来。研究表明，稳定的子集 血液中存在大量的microRNAs，这可能会影响其他组织或微生物 暴露在他们面前。在这个创新的项目中，我们的目标是探索人类血液的潜在作用 蚊子摄取的循环microRNA对蚊子基因表达的调节 以及它们对它们传播的病毒复制的影响。作为模型，我们将使用埃及伊蚊，一种 臭名昭著的媒介有几种虫媒病毒，而登革热病毒是第二大媒介传播病毒 病原体。我们的初步数据显示，血液来源的microRNA在蚊子中是稳定的 几个小时后，蚊子中肠成功地进入体腔内的其他组织，重要的是发生 在生物学上数量丰富。此外，我们的初步结果显示，至少有一名 人类血液中的microRNA改变了蚊子的基因，这些基因与蚊子的免疫和 繁殖。 我们假设(I)通过血液喂养获得的循环中的人类血源性miRNAs是 通过蚊子中肠吸收并转移到蚊子组织中，以及(Ii)交换的 MiRNAs在蚊子生物学中发挥作用，并影响它们传播的病毒的复制。 为了解决这些假设，我们的目标是1)分析Ae中的人血miRNAs。埃及伊蚊生物学，2) 目的：确定Ae中血液miRNAs的靶基因。埃及伊蚊及其对蚊子生物学的影响，以及 3)确定抑制人血miRNAs对蚊虫-病毒相互作用的影响。 我们预计，结果将促进我们对以下分子事件的理解 蚊子吸血和建立识别潜在目标的基本知识 干扰蚊子繁殖或病毒复制的分子。

PROJECT SUMMARY Small non-coding RNAs, in particular microRNAs, play significant roles in regulation of various biological processes and their dysregulation leads to disorders. Recently, their role in cell-cell and cross-species communications has also been revealed. Research has shown that a subset of stable microRNAs is present in high abundance in blood which may affect other tissues or microorganisms exposed to them. In this innovative project, we aim to explore the potential role of human blood circulating microRNAs taken up by mosquitoes in regulating expression of genes in the mosquitoes and their effect on replication of viruses that they transmit. As a model, we will use Aedes aegypti, a notorious vector of several arboviruses, and dengue virus as the second most important vector-borne pathogen. Our preliminary data shows that blood-derived microRNAs are stable in mosquitoes for hours, successfully pass the mosquito midgut into other tissues in the body cavity and importantly occur in biologically abundant numbers. In addition, our preliminary results show that at least one of the human blood microRNAs alter mosquito genes that are involved in mosquito immunity and reproduction. We hypothesize that (i) circulating human blood-derived miRNAs obtained through blood feeding are absorbed through the mosquito midgut and translocated into mosquito tissues, and (ii) the exchanged miRNAs play roles in mosquito biology and affect replication of viruses they transmit. To address these hypotheses, we aim 1) to analyze human blood miRNAs in Ae. aegypti biology, 2) to identify the target genes of blood miRNAs in Ae. aegypti and their effect on mosquito biology, and 3) determine the effect of inhibition of human blood miRNAs on mosquito-virus interactions. We anticipate that the outcomes will advance our understanding of the molecular events following blood uptake by mosquitoes, and build-up of essential knowledge in identification of potential target molecules for interfering in mosquito reproduction or virus replication.