Virology Core

病毒学核心

• 批准号: 10220700
• 负责人: Thomas C. Friedrich
• 金额: $ 28.95万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10220700
• 关键词: AIDS/HIV problem; Animals; Antibody-mediated protection; B-Lymphocytes; Biological; Biological Assay; Biology; Blood; Body Fluids; Complex; Data; Data Analyses; Dengue Virus; Flavivirus; Fluorescent in Situ Hybridization; Functional disorder; Funding; Genomics; Human Resources; Immune response; Immunity; Influenza; Lead; Liquid substance; Macaca; Measurement; Measures; Methods; Modeling; Molecular Diagnostic Testing; Monitor; Neonatal; Nucleic Acids; Outcome; Outcome Measure; Outcome Study; Pathogenesis; Pathology; Plaque Assay; Pregnancy; Prevalence; Primates; Production; RNA; Research; Research Personnel; Risk; Services; Specimen; Technical Expertise; Techniques; Time; Tissue Sample; Tissues; Urine; Validation; Viral; Viral Load result; Viremia; Virus; Virus Replication; Wisconsin; ZIKV infection; Zika Virus; antibody immunotherapy; design; experience; experimental study; fetal; fetal infection; in vivo; meetings; molecular diagnostics; neonatal outcome; nonhuman primate; novel; pregnant; primary endpoint; primary outcome; programs; virology

Virology Core - Project Summary/Abstract The overall objective of this Program Project is to understand the pathophysiology of Zika virus (ZIKV) infection in pregnancy. Three distinct, but synergistic Projects will examine different aspects of this overarching research problem. They will define the relationship between maternal viremia and risk of fetal infection and pathogenesis (Project 1), examine the impact of pre-existing immunity to dengue virus (DENV), a close relative of ZIKV, on the outcomes of ZIKV infection in pregnancy (Project 2), and determine whether antibody immunotherapy can reduce both maternal viremia and risk of fetal pathol- ogy (Project 3). Additionally, DENV- and ZIKV-naive pregnant macaques infected with ZIKV in Project 1 will serve as controls for the other Projects. Major outcome measures in all these experiments will include the level and duration of maternal ZIKV viremia and the level and dissemination of ZIKV in neo- natal tissues. Therefore, to allow for valid and robust comparisons across Projects, this P01 requires a well-characterized large-scale ZIKV challenge stock and validated measurements of ZIKV in biological specimens. Project 2 will similarly require a defined stock of DENV and validated assays to track DENV replication. The Virology Core will support all 3 Projects by providing these virus stocks and assays, as well as technical expertise in the interpretation of data. We will accomplish this through 4 specific aims: Specific Aim 1: Provide a characterized stock of ZIKV to each Project Specific Aim 2: Provide a characterized DENV-2 stock for Project 2 Specific Aim 3: Measure ZIKV burdens in body fluids and tissues for each Project Specific Aim 4: Measure DENV burdens in blood for Project 2 The Virology Core will be led by Dr. Thomas Friedrich, an expert in nonhuman primate virology and molecular diagnostics, who is also co-Investigator on Project 1. Dr. Matthew Aliota, junior Lead on Project 2, will serve as co-Investigator in the Virology Core, lending his expertise in flavivirus biology. The Virology Core will thus be tightly integrated with the entire P01.

病毒学核心-项目总结/摘要 该项目的总体目标是了解寨卡病毒（ZIKV）的病理生理学 妊娠期感染。三个不同的，但协同项目将审查这一不同方面 首要的研究问题。他们将确定母体病毒血症和妊娠风险之间的关系。 胎儿感染和发病机制（项目1），检查先前存在的登革热免疫力的影响 ZIKV的近亲DENV对妊娠期ZIKV感染结局的影响（项目2），以及 确定抗体免疫治疗是否可以降低母体病毒血症和胎儿病理风险， ogy（项目3）。此外，在项目中，用ZIKV感染DENV-和ZIKV-幼稚的怀孕猕猴， 1将作为其他项目的对照。所有这些实验的主要结果指标将 包括母体ZIKV病毒血症的水平和持续时间以及新生儿中ZIKV的水平和传播。 纳塔尔组织因此，为了在项目之间进行有效和可靠的比较，本P01需要 充分表征的大规模ZIKV攻击储备液和生物学中ZIKV的经验证的测量 标本项目2同样需要DENV的确定库存和经验证的检测方法来跟踪DENV 复制的病毒学核心将通过提供这些病毒储备和检测来支持所有3个项目， 以及解释数据的技术专长。我们将通过四个具体目标来实现这一目标： 具体目标1：为每个项目提供ZIKV的特征化库存 具体目标2：为项目2提供表征的DENV-2原液 具体目标3：测量每个项目的体液和组织中的ZIKV负荷 具体目标4：测量项目2血液中的DENV负荷 病毒学核心将由非人灵长类病毒学专家托马斯·弗里德里希博士领导， 分子诊断学，他也是项目1的共同研究者。Matthew Aliota博士，初级领导 项目2将担任病毒学核心的共同研究者，以他在黄病毒生物学方面的专业知识。 因此，病毒学核心将与整个P01紧密集成。