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.

病毒核心 - 项目摘要/摘要 该计划项目的总体目的是了解寨卡病毒的病理生理（ZIKV） 怀孕感染。三个不同的，但协同的项目将研究其中的不同方面 总体研究问题。他们将定义孕产妇病毒血症和风险之间的关系 胎儿感染和发病机理（项目1），检查先前存在的免疫对登革热的影响 病毒（DENV），ZIKV的亲戚，关于怀孕ZIKV感染的结果（项目2）和 确定抗体免疫疗法是否可以降低母体病毒血症和胎儿病态的风险 OGY（项目3）。此外，在项目中感染了ZIKV 1将作为其他项目的控制。所有这些实验中的重大结果指标将 包括母体ZIKV病毒血症的水平和持续时间，以及ZIKV的水平和传播 出生组织。因此，为了允许在项目之间进行有效且可靠的比较，此P01需要一个 特征良好的大规模ZIKV挑战库存和经过验证的ZIKV测量 标本。项目2类似地需要定义的DENV库存和经过验证的测定来跟踪DENV 复制。病毒学核心将通过提供这些病毒库存和测定法来支持所有3个项目， 以及数据解释方面的技术专长。我们将通过4个特定目标来实现这一目标： 特定目标1：为每个项目提供特征的ZIKV库存 特定目标2：为项目2提供特征的DENV-2股票 特定目标3：测量每个项目的ZIKV负担在体液和组织中 特定目标4：测量项目2的血液中的DENV负担 病毒学核心将由非人类灵长类动物病毒学专家Thomas Friedrich博士领导 Molecular Diagnostics，他也是项目1的共同研究者。MatthewAliota博士 项目2将作为病毒核心的共同评估者，在Flavivirus Biology方面提供专业知识。 因此，病毒学核心将与整个P01紧密整合。