Alphaviral Determenants of Infection in Mice and Vectors

翻译后摘要：东部，委内瑞拉和西部马脑炎（马脑炎，VEE，WEE）病毒（甲病毒; 披膜病毒科）是蚊子传播的病毒，在人类和马中引起严重的脑炎。所有三 病毒被NIAID和CDC列为B类病原体，并被列为潜在的生物恐怖主义/生物战 (BT/BW）代理。关于传播潜力、蚊子宿主、 决定因素、气溶胶化病毒的发病机制、获得性和先天性免疫应答等 一组病毒，特别是EEEV和WEEV。在本项目中，我们将开发甲病毒（EEEV和WEEV） 感染性cDNA克隆，以确定病毒在小鼠中复制和发病的分子机制 以及在BT/BW事件期间可能作为二次传播媒介的蚊子的传染性。 我们还将开发稳定的双亚基因组EEEV、VEEV和WEEV转导病毒， 表征它们在感染的小鼠和载体中复制和表达报告基因的能力。我们还将 进行发病机制研究，主要集中在EEEV和WEEV的小动物模型，但也将 包括来自三种甲病毒的转导病毒。我们将集中在发病机制， 通过载体和气溶胶感染途径感染小鼠。最后，我们将描述病毒载体 所有三种病毒的相互作用可能导致BT/BW媒介传播潜力增加 病原体和新出现的甲病毒病原体。 项目互动：项目的Pi是Ann M.鲍尔斯和肯·E.奥尔森鲍尔斯博士和 奥尔森位于疾病控制中心，病媒传染病部， 节肢动物传播的传染病实验室（CSU）在柯林斯堡，有限公司，分别鲍尔斯博士和 奥尔森在甲病毒生物学、分子生物学、载体生物学方面都有相当丰富的经验， 发展甲病毒与小动物模型相互作用的专业知识。此外，该项目还将与 和其他调查员一起工作具体而言，与Kedl、Blair和Dow博士一起进行Lanacs研究（II.C.6）， Drs. Titus and Beaty（II.B.2.）和Chang博士（II.B.3）介绍新疫苗技术，Morrey博士（II.G）介绍 分享本项目开发的感染性甲病毒克隆和转导病毒，Fujinami博士和 Foy（II.H.2）关于基于RNAi的抗病毒疗法。该项目将成为制定协议的资源， 病毒和试剂，可以使用的其他成员的RCE。最后，该项目将依赖于 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: Eastern, Venezuelan, and Western equine encephalitis (EEE, VEE, WEE) viruses (Alphavirus; Togaviridae) are mosquito-borne viruses causing severe encephalitis in humans and horses. All three viruses are listed as category B agents by both NIAID and CDC and as potential bioterrorism/biowarfare (BT/BW) agents. There are enormous knowledge gaps concerning transmission potential, mosquito-host determinants, pathogenesis from aerosolized virus, acquired and innate immune responses, etc. for this group of viruses, especially EEEV and WEEV. In this project, we will develop alphavirus (EEEV and WEEV) infectious cDNA clones to determine molecular mechanisms of viral replication and pathogenesis in mice and infectivity of mosquitoes that may serve as vectors in secondary transmission during a BT/BW event. We will also develop stable, double subgenomic EEEV, VEEV, and WEEV transducing viruses to characterize their ability to replicate and express a reporter gene in infected mice and vectors. We will also conduct pathogenesis studies focusing primarily on EEEV and WEEV in small animal models, but will also include transducing viruses from the three alphaviruses in these studies. We will focus on pathogenesis in mice following infection by vector and aerosol routes of infection. Finally we will characterize virus-vector interactions for all three viruses that may lead to increased transmission potential by vectors of BT/BW agents and emerging alphavirus pathogens. Project Interactions: The Pi's of the project are Drs. Ann M. Powers and Ken E. Olson. Drs. Powers and Olson are located at the Centers for Disease Control, Division of Vector-borne Infectious Diseases and Arthropod-borne Infectious Diseases Laboratory (CSU) in Fort Collins, Co., respectively. Dr. Powers and Olson both have considerable experience in alphavirus biology, molecular biology, vector biology and are developing expertise in alphavirus interactions with small animal models. In addition, the project will interact with other investigators in the RCE. Specifically, with Drs. Kedl, Blair, and Dow on Lanacs studies (II.C.6), Drs. Titus and Beaty (II.B.2.) and Dr. Chang (II.B.3) on novel vaccine technologies, Dr. Morrey (II.G) in sharing infectious alphavirus clones and transducing viruses developed in this project and Dr. Fujinami and Foy (II.H.2) on RNAi-based antiviral therapies. This project will be a resource for developing protocols, viruses, and reagents that can be used by other members of the RCE. Finally, this project will be dependent on two SFC's: Animal Models Core (III.A) and Genomics/Proteomics Core (III.C).