Core 2: Virology Core

核心 2：病毒学核心

• 批准号: 9319888
• 负责人: Ann M Chahroudi
• 金额: $ 49.41万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-24 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9319888
• 关键词: Albumins; Anatomy; Animal Experiments; Animal Model; Animals; Anti-Retroviral Agents; Biological Assay; Blinded; CD8-Positive T-Lymphocytes; Cell Culture Techniques; Cells; Collaborations; Complex; DNA; Data; Defective Viruses; Detection; Evolution; Frequencies; Goals; Gold; HIV; Human; Human Resources; Immune; Immunologics; Infant; Infection; Institutes; Interruption; Intervention; Kinetics; Laboratories; Lead; Location; Macaca mulatta; Measures; Methods; Modeling; Monkeys; Oral; Pattern; Phylogenetic Analysis; Plasma; Plasma Cells; Positioning Attribute; Production; Quantitative Reverse Transcriptase PCR; RNA; Regimen; Reproducibility; Reverse Transcriptase Polymerase Chain Reaction; SIV; Sampling; Sensitivity and Specificity; Sequence Analysis; Site; Specimen; Standardization; Statistical Data Interpretation; T-Lymphocyte Epitopes; Techniques; Testing; Therapeutic; Therapeutic Effect; Time; Tissues; Universities; Vaccines; Variant; Viral; Viral Genome; Viral Load result; Viremia; Virus; Virus Replication; Work; base; deep sequencing; genome analysis; immunological intervention; intervention effect; mathematical model; meetings; model development; neutralizing antibody; next generation sequencing; nonhuman primate; novel; passive antibodies; potential biomarker; programs; response; simian human immunodeficiency virus; tool; viral rebound; virology; whole genome

ABSTRACT – Virology Core (Core 2, Leader: Dr. Ann Chahroudi, Emory University) Achieving the proposed Program's goal requires precise quantitation and characterization of SHIV reservoirs and viral dynamics. The Virology Core's objective is to support the Program's two Projects in the rigorous testing of their central hypotheses by providing state-of-the-art virological tools including (i) quantitative PCR analyses of cell-associated SHIV DNA and RNA and plasma SHIV RNA, (ii) combined cell culture and PCR- based assays quantifying the proportion of replication-competent viruses, and (iii) viral sequence analyses by deep sequencing and single genome analysis (SGA). The Virology Core will be led by Dr. Chahroudi, with both routine and novel assays performed in her laboratory at Emory University, and in collaboration with Duke sequencing expertise to provide standardized techniques across Projects 1 & 2 that will permit the ascertainment of interpretable and generalizable results. The Core proposes the following Specific Aims: 1) Quantitative PCR analysis of viral loads in plasma and cells. 2) Estimation of the reservoir size by quantification of replication-competent / inducible virus; and 3) Sequence analyses of pre-ART and rebound viremia in comparison to cell-associated SHIV variants during ART and at rebound. These Aims will make use SIV/SHIV quantification assays developed by Dr. Chahroudi's laboratory and rigorously evaluated for sensitivity, specificity and reproducibility in the animal model to be used, as well as SIV/HIV sequencing expertise of the Duke Human Vaccine Institute. The Virology Core will serve both Projects and interact with both the Administrative and Statistical Core and the Nonhuman Primate Core of this Program to achieve our shared goals. The Virology Core is thus strongly positioned to generate reliable and quantifiable data to rigorously assess the origin, predictors, and virologic correlates of viral rebound in this Program.

摘要-病毒学核心(核心2，领导者：埃默里大学Ann Chahroudi博士) 实现拟议计划的目标需要对Shiv储集层进行精确的量化和描述 和病毒动力学。病毒学核心的目标是支持该计划的两个项目 通过提供最先进的病毒学工具来检验他们的中心假设，包括(I)定量聚合酶链式反应 细胞相关SHV DNA、RNA和血浆SHV RNA的分析(II)细胞培养和聚合酶链式反应- 基于量化可复制病毒比例的分析，以及(Iii)通过以下方式进行病毒序列分析 深度测序和单基因组分析(SGA)。病毒学核心将由Chahroudi博士领导，两者都 在她在埃默里大学的实验室里，并与杜克大学合作，进行了常规和新颖的分析 提供跨项目1和2的标准化技术的排序专业知识，这将允许 确定可解释的和可概括的结果。《核心》提出了以下具体目标：1) 血浆和细胞病毒载量的定量聚合酶链式反应分析。2)通过以下方式估计储油层大小 可复制/可诱导病毒的量化；以及3)前ART和反弹的序列分析 抗逆转录病毒治疗期间和反弹时病毒血症与细胞相关的SIV变异体的比较。这些目标将会利用 SIV/SIV定量分析由Chahroudi博士的实验室开发，并严格评估 所用动物模型的敏感性、特异性和重复性，以及SIV/HIV测序 杜克人类疫苗研究所的专业知识。病毒学核心将为这两个项目服务，并与 本程序的行政和统计核心以及非人类灵长类核心，以实现我们的 共同的目标。因此，病毒学核心在生成可靠和可量化的数据方面处于有利地位 严格评估本计划中病毒反弹的来源、预测因素和病毒学相关性。