Biology of Vector/Aerosol Transmission of Bunyaviridae

布尼亚病毒科载体/气溶胶传播的生物学

• 批准号: 7310298
• 负责人: RICHARD GRAEME TITUS
• 金额: $ 24.68万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7310298
• 关键词: Biology; Vector; Aerosol; Transmission; Bunyaviridae

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.).

翻译后摘要：节肢动物和啮齿动物传播的病毒在家庭布尼亚病毒代表了严重的威胁 对人类和动物的健康都有影响。最近出现的大多数病毒都来自这个家族， 布尼亚病毒科作为生物恐怖主义（BT）的代理人有很大的潜力。例如，裂谷热病毒是 被许多人认为是最佳的BT代理，因为它能够出现在新的领域， 不仅对人类而且对动物群体，并且容易通过气溶胶传播。尽管有这些 事实上，目前还没有针对布尼亚病毒的安全有效的疫苗，尤其是针对人类的疫苗。 在这个项目中，我们将使用特征良好的长曲棍球病毒（LACV）系统来分析 LACV通过气溶胶或蚊媒水平传播感染的发病机制。我们 将为布尼亚病毒科开发LACV载体和气溶胶传播小鼠模型。此外，我们将 确定蚊子唾液对LACV的深刻疾病增强作用的机制 传染性和负责这种现象的唾液蛋白。有了这些信息，我们将 然后设计疫苗（例如，辛德毕斯复制子，LANAC），将保护免受气溶胶或蚊子传播 LACV和布尼亚病毒科中的其它虫媒病毒以及选定的汉坦病毒的气溶胶感染。 项目互动：该项目将与RCE的其他组成部分以及 RCE之外的合作者（Valenzuela博士，NIH）。该项目的PI是理查德·泰特斯博士和巴里博士 比蒂Titus和Beaty位于病理学大楼和节肢动物和传染病 实验室，分别。Titus博士提供动物模型/节肢动物唾液增强，而Beaty博士 为项目提供病毒学/蚊子生命周期专业知识;因此，该项目之所以可能， 两个群体之间的互动。此外，该项目还将与其他 RCE的调查员。具体而言，与Kedl、Blair、Dow博士一起进行LANAC研究（II.C.6.）奥尔森博士和 权力（二. B.）关于虫媒病毒发病机理和复制子研究，Barnard博士（II.G.4.）在布尼亚病毒模型上， 以及丹迪和格兰杰博士（H.B.6.），以及孢子2和孢子1中的其他项目。此外，该项目 将取决于2个SFC：动物模型核心（III. A.）和Genomics/Proteomics Core（III.C.）。