TICK DETERMINANTS OF POWASSAN VIRUS TRANSMISSION

波瓦桑病毒传播的蜱决定因素

• 批准号: 9903213
• 负责人: Saravanan Thangamani
• 金额: $ 40.5万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9903213
• 关键词: Antibodies; Antigens; Attenuated; Bite; Black-legged Tick; Blood; Canada; Cells; Cellular Immunology; Cellular Infiltration; Centers for Disease Control and Prevention (U.S.); Chemosensitization; Collection; Complex; Cutaneous; Data; Dengue; Development; Disease; Disease Outbreaks; Disease Vectors; Ebola virus; Encephalitis; Environment; Flavivirus; Foundations; Future; Geography; Goals; Hour; Human; Immune; Immune response; Immunologics; Immunophenotyping; Infection; Inflammatory; Investigation; Japanese Encephalitis; Kinetics; Knowledge; Lasers; Lead; Location; Lyme Disease; Massachusetts; Molecular; Molecular Genetics; Molecular Immunology; Mus; Names; Neurologic; New Hampshire; New Jersey; Pathogenesis; Patients; Pharmacology; Plasmids; Powassan encephalitis; Powassan virus; Prevalence; Process; Production; Proteins; Public Health; Reporting; Research; Role; Salivary; Salivary Glands; Salivary Proteins; Scanning; Site; Skin; Survivors; Systems Biology; Technology; Testing; Tick Control; Tick-Borne Diseases; Tick-Borne Encephalitis; Tick-Borne Encephalitis Virus; Ticks; Time; United States; Up-Regulation; Vaccines; Vector-transmitted infectious disease; Virus; Virus Diseases; West Nile virus; Work; Yellow Fever; ZIKA; Zika Virus; chemokine; comparative; cytokine; feeding; genetic epidemiology; immunogenic; immunoregulation; improved; innovation; member; mosquito-borne; nervous system disorder; novel; pathogen; salivary gene; tick bite; tick feeding; tick saliva; tick-borne; transmission process; vector; viral transmission

Project Summary: Tick borne diseases continue to emerge in the United States. Powassan virus (POWV), transmitted by the Lyme disease vector Ixodes scapularis, is a member of the tick-borne encephalitis virus (TBEV) complex. It causes encephalitis, including fatal neuroinvasive disease in approximately 10% of cases, and long-lasting neurological sequelae have been documented in 50% of survivors. POWV has recently re-emerged, as evident by the increase in number and expanding geographic range of confirmed cases (USGS, 2015; CDC). POWV transmitted to humans by infected ticks, and successful transmission of POWV can occur within three hours of Ixodes scapularis attachment. Successful tick feeding is facilitated by a collection of pharmacologically active factors/proteins in tick saliva, which are secreted into the feeding pool that the tick creates on the vertebrate host. The skin serves as the interface of host-virus-tick interactions; therefore, the objective of this proposal is to investigate cutaneous host immunomodulation by POWV-infected ticks while examining components of tick saliva that lead to a more favorable environment for virus transmission, and identify salivary components that enhances POWV infection. We will test our hypothesis by exploring the following specific aims: (1) Investigate the role of POWV infected tick saliva in modulating immune responses at the bite site to facilitate POWV transmission and dissemination; (2) Identify the specific tick salivary protein/s that potentiate POWV transmission. The proposed research is innovative and novel because we, for the first time, will examine the molecular mechanisms involved in potentiation of a tick borne virus at the tick-host interface. We will also investigate concurrently both host and vector attributes of POWV infection using a systems biology approach. This has never been attempted before. The proposed project will also identify POWV infected cells at the site of tick feeding using Laser Scanning Cytometer that will provide us with precise identification of the type, number, time, and location of immune cells associated with early tick feeding time points. We will also identify the salivary protein/s that enhances POWV infection and dissemination, and also check if antibodies to these proteins will attenuate virus infection. This proposed work will make a significant contribution to the field because it will employ systems biology approach, cutting-edge technologies and innovative ideas to understand the mechanisms and identify salivary components that lead to a more favorable environment for tick-borne virus transmission. Overall, these studies will fill the gaps in our current knowledge/understanding of tick-borne viral infection that continues to increase in prevalence, and provide a new line of investigation of the tick-pathogen-host interface. This, in turn, will lead to development of countermeasures that will attenuate the virus infection.

项目总结： 壁虱传播的疾病在美国继续出现。波瓦桑病毒(POWV)，由 莱姆病病媒肩部硬蜱是森林脑炎病毒复合体的一员。它 导致脑炎，包括约10%的病例中致命的神经侵袭性疾病，并持续时间长 50%的幸存者有神经后遗症的记录。POWV最近重新出现，这是显而易见的 由于确诊病例数量的增加和地域范围的扩大(USGS，2015；CDC)。POWV 通过受感染的扁虱传播给人类，成功传播POWV可在三小时内发生 肩胛骨附着性硬体动物。成功的扁虱喂养是由一系列药理活性物质促进的 壁虱唾液中的因子/蛋白质，分泌到壁虱在脊椎动物身上产生的喂食池中。 主持人。皮肤充当宿主-病毒-扁虱相互作用的界面；因此，这项提议的目标是 检测硬蜱成分的同时，研究感染POWV的硬蜱对皮肤宿主的免疫调节作用 唾液导致更有利的病毒传播环境，并识别唾液成分 增强POWV感染。我们将通过探索以下具体目标来检验我们的假设：(1)调查 口蹄疫病毒感染的硬蜱唾液对咬合点免疫反应的调节作用 传播和传播；(2)确定特定的扁虱唾液蛋白/增强POWV的S 变速箱。这项拟议的研究具有创新性和新颖性，因为我们将首次研究 壁虱传播病毒在壁虱-宿主界面增强的分子机制。我们还将 使用系统生物学方法同时研究POWV感染的宿主和媒介属性。 这是以前从未尝试过的。拟议的项目还将在现场识别受战俘病毒感染的细胞。 用激光扫描细胞仪采集的扁虱，这将为我们提供精确的类型识别， 与早期扁虱饲养时间点相关的免疫细胞的数量、时间和位置。我们还将确定 增强POWV感染和传播的唾液蛋白/S，并检查针对这些的抗体 蛋白质将减弱病毒感染。这项拟议的工作将对该领域作出重大贡献。 因为它将采用系统生物学的方法、尖端技术和创新思想来 了解机制并确定唾液成分，使环境更有利 壁虱传播的病毒。总体而言，这些研究将填补我们目前对 壁虱传播的病毒感染继续增加，并提供了一条新的调查路线 扁虱-病原体-寄主界面。这反过来又将导致制定对策，以减弱 病毒感染。