Virology Core

病毒学核心-项目摘要/摘要 本项目的总体目标是了解寨卡病毒(ZIKV)的病理生理学 孕期感染。三个不同但协同的项目将考察这一问题的不同方面 首要的研究问题。他们将确定母体病毒血症与 胎儿感染和发病机制(项目1)，检查先前存在的免疫对登革热的影响 寨卡病毒的近亲--登革热病毒(DENV)对妊娠期间感染寨卡病毒的结局的影响(项目2)，以及 确定抗体免疫疗法是否可以同时降低母亲病毒血症和胎儿病变的风险- OGY(项目3)。此外，项目中感染ZIKV的DENV和ZIKV幼稚怀孕猕猴 1将作为其他项目的控制。所有这些实验中的主要结果衡量标准都将 包括母体ZIKV病毒血症的水平和持续时间以及ZIKV在新生婴儿中的水平和传播 生下来的组织。因此，为了允许跨项目进行有效和可靠的比较，本P01需要一个 规模化ZIKV挑战库及ZIKV在生物上的有效测量 标本。项目2将同样需要定义的DENV库存和有效的分析来跟踪DENV 复制。病毒学核心将通过提供这些病毒库存和分析来支持所有3个项目，如 以及在数据解释方面的技术专长。我们将通过四个具体目标来实现这一目标： 具体目标1：为每个项目提供具有特色的ZIKV库存 具体目标2：为项目2提供特色化的DENV-2库存 具体目标3：为每个项目测量体液和组织中的ZIKV负荷 具体目标4：为项目2测量血液中的DENV负担 病毒学核心将由托马斯·弗里德里希博士领导，他是非人灵长类病毒学和 分子诊断学，同时也是项目1的联合调查员。 项目2将担任病毒学核心的联合调查员，利用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紧密结合。

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.