The role of hemocytes in mosquito arbovirus infection

项目总结 蚊虫传播病毒导致数亿人感染，其中每一种都有重大疾病 发病率和死亡率结果。然而，尽管蚊子宿主对病毒复制有要求 和传播，我们对这些机制的了解很少。这包括 蚊子免疫细胞或血细胞，可能对病毒复制有积极和消极影响。 基于我们在血细胞生物学和宿主-病原体相互作用方面的专业知识，我们现在希望研究这种作用 蚊子血细胞对登革热(DENV)和寨卡病毒(ZIKV)感染的影响。使用化学遗传学方法， 我们提供的初步数据表明，我们有能力耗尽伊蚊的吞噬免疫细胞群 埃及人，这是我们提议的实验的基础。因此，这项建议中的研究将 检测吞噬免疫细胞在DENV和ZIKV感染中的作用，并探讨 这些细胞在蚊子宿主中介导系统RNAi反应的机制(目标1)。在……里面 此外，我们还将探索血细胞作为病毒扩增的第二部位的潜在作用，这可能 提高病毒滴度和帮助传播，以增加传播的可能性(目标2)。一起，我们期待着 这项研究的结果将为研究蚊子体内病毒复制的机制提供新的信息 寄主并确定血细胞在蚊媒抵抗虫媒病毒感染能力中的不可或缺的作用。

PROJECT SUMMARY Mosquito arbovirus transmission causes hundreds of millions of human infections every with significant disease morbidity and mortality outcomes. However, despite the requirements of the mosquito host for virus replication and transmission, our understanding of these mechanisms is poorly understood. This includes the role of mosquito immune cells, or hemocytes, which may have both positive and negative influences on virus replication. Building on our expertise in hemocyte biology and host-pathogen interactions, we now look to examine the role of mosquito hemocytes on dengue (DENV) and Zika virus (ZIKV) infection. Using a chemical genetics approach, we provide preliminary data demonstrating our ability to deplete phagocytic immune cell populations in Aedes aegypti, which serve as the basis of our proposed experiments. Therefore, the studies in this proposal will examine the contributions of phagocytic immune cells on DENV and ZIKV infections, and explore the mechanisms by which these cells may mediate systemic RNAi responses in the mosquito host (Aim 1). In addition, we will also explore potential roles of hemocytes as a secondary site of virus amplification that may increase viral titers and aid dissemination to increase the likelihood of transmission (Aim 2). Together, we expect that the results of this study will provide new information into the mechanisms of virus replication in the mosquito host and define the integral role of hemocytes in mosquito vector competence to arbovirus infection.