Biology of Vector/Aerosol Transmission of Bunyaviridae

摘要：布尼亚病毒科的节肢动物传播和啮齿动物传播的病毒是一种严重的威胁。 对人类和动物的健康都有好处。最近出现的大多数病毒都来自这个家族，许多 布尼亚病毒科具有作为生物恐怖主义(BT)病原体的巨大潜力。例如，裂谷热病毒是 被许多人认为是最佳的Bt代理人，因为它有能力在新的领域出现，而不是致命的 不仅对人类，而且对动物种群也是如此，并很容易通过气雾剂传播。尽管如此 事实上，几乎没有安全或有效的本雅型病毒疫苗--特别是针对人类的疫苗。 在这个项目中，我们将使用特征良好的君越病毒(LACV)系统来分析 气雾剂或蚊媒水平传播LACV的发病机制。我们 将为布尼亚病毒科开发LACV媒介和气溶胶传播小鼠模型。此外，我们还将 确定蚊子唾液对LACV的深刻致病作用的机制 传染性和导致这种现象的唾液蛋白质。有了这些信息，我们将 然后设计疫苗(如Sindbis复制子，LANAC)，以防止气雾剂或蚊子传播 布尼亚病毒科中的LACV和其他虫媒病毒，以及部分汉坦病毒的气溶胶感染。 项目互动：该项目将与RCE的其他组件以及 RCE之外的合作者(NIH瓦伦苏埃拉博士)。该项目的负责人是理查德·蒂图斯博士和巴里博士 比蒂。泰图斯博士和贝蒂博士位于病理大楼和节肢动物与传染病 分别在实验室。泰特斯博士提供了动物模型/节肢动物唾液增强，而比蒂博士提供了 为该项目提供病毒学/蚊子生命周期专业知识；因此，该项目只有在以下情况下才有可能 这两个群体之间将会发生的互动。此外，该项目还将与其他 皇家空军司令部的调查人员。具体地说，与Kedl、Blair、Dow博士关于LANAC的研究(II.C.6.)奥尔森博士和 权力(II.B.)关于虫媒病毒的致病机制和复制子研究，Barnard博士(II G.4)在布尼亚病毒模型上， 和Dr.Dandy and Grainger(H.B.6)，以及孢子2号和孢子1号的其他项目。此外，这个项目 将依赖于两个SFC：动物模型核心(III.A.)和基因组学/蛋白质组学核心(III.C.)。

Abstract: Arthropod-borne and Rodent-borne viruses in the family Bunyaviridaes represent a serious threat to both human and animal health. Most recently emerged viruses are from this family and many Bunyaviridae have significant potential as bioterrorism (BT) agents. For example, Rift Valley Fever virus is considered by many to be an optimal BT agent because of its ability to emerge in new areas, to be lethal not only for humans but also for animal populations, and to be readily transmitted via aerosol. Despite these facts, there are virtually no safe or effective vaccines for bunyaviruses - especially vaccines for humans. In this project we will use the well-characterized LaCrosse virus (LACV) system to analyze the pathogenesis of infection of LACV transmitted either by aerosol or horizontally by the mosquito vector. We will develop LACV vector and aerosol transmission mouse models for the Bunyaviridae. In addition, we will determine the mechanism underlying the profound disease-enhancing effects of mosquito saliva for LACV infectivity and the salivary proteins responsible for this phenomenon. Armed with this information, we will then design vaccines (eg, Sindbis replicon, LANACs) that will protect against aerosol or mosquito-delivered LACV and other arboviruses in the Bunyaviridae as well as aerosol infection with selected Hantaviruses. Project Interactions: This project will interact extensively with other components of the RCE and with collaborators outside the RCE (Dr. Valenzuela, NIH). The Pis of the project are Drs. Richard Titus and Barry Beaty. Drs. Titus and Beaty are located in the Pathology building and Arthropod and Infectious Disease Laboratory, respectively. Dr. Titus provides the animal model/arthropod salivary potentiation while Dr. Beaty provides the virology/mosquito life cycle expertises to the project; thus, the project is only possible because of the interactions that will occur between the two groups. In addition, the project will interact with other investigators in the RCE. Specifically, with Drs. Kedl, Blair, Dow on LANACs studies (II.C.6.) Drs. Olson and Powers (II.B.) on arbovirus pathogenesis and replicon studies, Dr. Barnard (II.G.4.) on bunyavirus models, and Drs. Dandy and Grainger (H.B.6.), and other projects in Spore 2 and PORE 1. In addition, this project will be dependent upon 2 SFCs: Animal Models Core (III.A.) and Genomics/Proteomics Core (III.C.).