Exploring the effect of human blood microRNAs on mosquito biology

探索人类血液 microRNA 对蚊子生物学的影响

• 批准号: 9805744
• 负责人: Sassan Asgari
• 金额: $ 16.2万
• 依托单位: UNIVERSITY OF QUEENSLAND
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9805744
• 关键词: Address; Aedes; Affect; Animals; Arboviruses; Bacteria; Bioinformatics; Biological; Biological Markers; Biological Process; Biology; Blood; Body Fluids; Cells; Chikungunya virus; Clinical Research; Communication; Culicidae; Data; Dengue Infection; Dengue Virus; Development; Diagnosis; Disease; Distant; Drug Metabolic Detoxication; Erythrocytes; Eukaryota; Event; Exposure to; Fat Body; Fertility; Gene Expression; Gene Expression Regulation; Genes; Hour; Human; Human body; Immunity; Impairment; Infection; Knowledge; Lead; Macromolecular Complexes; Malaria; Malignant Neoplasms; Membrane; Metabolism; MicroRNAs; Midgut; Modeling; Molecular; Organism; Outcome; Parasites; Plasmodium falciparum; Play; Production; Regulation; Reproduction; Research; Resistance; Ribosomes; Role; Sickle Cell; Site; Small RNA; Symbiosis; Taxonomy; Time; Tissues; Translational Repression; Untranslated RNA; Vesicle; Virus; Virus Replication; Wolbachia; Yellow fever virus; Zika Virus; body cavity; circulating microRNA; endosymbiont; feeding; inhibitor/antagonist; innovation; microorganism; pathogen; pathogenic virus; prediction algorithm; transcriptome; uptake; vector; vector-borne pathogen; viral transmission

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.

项目摘要 小的非编码RNA，特别是microRNA，在调节多种细胞因子中起重要作用。 生物过程及其失调导致疾病。最近，它们在细胞-细胞和 跨物种通信也已被揭示。研究表明，一个稳定的 microRNA在血液中以高丰度存在，可能会影响其他组织或微生物 暴露在他们面前。在这个创新项目中，我们的目标是探索人类血液的潜在作用， 蚊子在调节蚊子基因表达中摄取的循环microRNA 以及它们对所传播病毒复制的影响。作为一个模型，我们将使用埃及伊蚊， 几种虫媒病毒的臭名昭著的载体，和登革病毒作为第二个最重要的载体传播 病原体我们的初步数据显示，血液来源的microRNA在蚊子体内是稳定的， 小时，成功地通过蚊子中肠进入体腔中的其他组织， 在生物学上数量丰富。此外，我们的初步结果表明，至少有一个 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有关， 生殖 我们假设（i）通过血液喂养获得的循环人类血液来源的miRNA是 通过蚊子中肠吸收并易位到蚊子组织中，和（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中的人血液miRNAs。埃及生物学，2） 目的：筛选Ae.埃及伊蚊及其对蚊子生物学的影响， 3)确定人血miRNA对蚊子-病毒相互作用的抑制作用。 我们预计，这些结果将促进我们对以下分子事件的理解 蚊子的血液吸收，以及在确定潜在目标方面积累必要的知识 干扰蚊子繁殖或病毒复制的分子。