Core - Animal Model

核心-动物模型

• 批准号: 7899492
• 负责人: THOMAS W NORTH
• 金额: $ 70.36万
• 依托单位: J. DAVID GLADSTONE INSTITUTES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-15 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7899492
• 关键词: AIDS therapy; Accreditation; Address; Aftercare; American; Anatomy; Animal Model; Animals; Anti-Retroviral Agents; Antiviral Agents; Antiviral Therapy; Autopsy; Binding Sites; Biopsy; Blood; CD4 Positive T Lymphocytes; California; Caring; Cells; Clinical; Collaborations; Development; Diagnosis; Disease; Drug Combinations; Enhancers; Equipment and supply inventories; Exhibits; Functional disorder; Gene Expression; Goals; HIV; HIV-1; Highly Active Antiretroviral Therapy; Housing; Human; In Vitro; Individual; Infection; Investigation; Laboratory Animals; Licensing; Lymphoid; Lymphoid Cell; Macaca; Macaca mulatta; Modeling; Molecular; Molecular Weight; Monitor; NF-kappa B; Organ; Participant; Pathogenesis; Pathologist; Pathology; Pattern; Peptide Hydrolases; Pharmaceutical Preparations; Pharmacotherapy; Play; Primates; Principal Investigator; Property; Proteins; RNA; RNA-Directed DNA Polymerase; Regulation; Research; Research Infrastructure; Role; SIV; Sampling; Site; System; Systems Analysis; T-Lymphocyte; Testing; Time; Tissue Sample; Tissues; Transcript; Transcriptional Activation; Treatment Failure; Treatment Protocols; Vaccine Therapy; Veterinarians; Viral; Viral Genes; Viral load measurement; Viremia; Virus; Virus Activation; Virus Latency; animal care; animal data; antiretroviral therapy; base; in vivo; lymph nodes; nonhuman primate; novel; peripheral blood; programs; research study; simian human immunodeficiency virus; tissue culture; viral DNA

This Program Project conducts a comprehensive analysis of the mechanism(s) of HIV latency and viral reservoirs. In vitro investigations in tissue culture systems (Projects 1, 2, and 3) will be closely coordinated with in vivo studies in Core B ("Non-human Primates for HIV/SIV Reservoirs and Latency"). Accordingly, Core B will provide rhesus macaques and appropriate infrastructure support required for the animal model studies in this Program Project. This Core uses macaques housed at the California National Primate Research Center (CNPRC) at UC Davis. This Center is accredited by the American Association for Accreditation of Laboratory Animal Care (AAALAC) and includes full-time, licensed veterinarians. Appropriate facilities and expertise are available for the care and handling of macaques inoculated with SIV/SHIV at biosafety levels 2 and 3 (BSL-2, -3). In addition, the CNPRC infrastructure and staff provide for clinical analysis of infected animals; this includes physical diagnosis, microbiological analysis, and hematological assessments. Veterinary pathologists perform comprehensive necropsy and pathology analysis and to collect tissues and organs for all of the projects in this Program. Several studies on antiretroviral drugs, in the SIV/macaque and RTSHIV/ macaque systems, have been conducted at the CNPRC; thus, this Core builds on demonstrated strengths that are directly relevant to the goals of the Program Project. For the studies in Core B, we hypothesize that the macaque model of SIV/SHIV infection can be used to define viral reservoirs, to analyze latency, and to study activation of virus in vivo. Three Specific Aims address this hypothesis: Aim 1: to define conditions in the SIV/macaque and RT-SHIV/macaque systems for analysis of viral latency/reservoirs as observed in humans infected with HIV; Aim 2: to analyze virus localization in infected macaques undergoing antiretroviral therapy; Aim 3: to determine the role of viral and host-cell factors in the regulation of viral latency, persistence, and reactivation.

该计划项目对艾滋病毒潜伏期和病毒的机制进行了全面分析。 水库。将密切协调组织培养系统的体外研究（项目 1、2 和 3） 核心 B 的体内研究（“非人类灵长类动物的 HIV/SIV 储库和潜伏期”）。因此， 核心B将提供恒河猴和动物模型所需的适当基础设施支持 在此计划项目中进行研究。该核心使用加州国家灵长类研究中心饲养的猕猴 加州大学戴维斯分校中心（CNPRC）。该中心获得美国认证协会认证 实验动物护理 (AAALAC)，包括全职、有执照的兽医。适当的设施和 具备在生物安全级别 2 下护理和处理接种 SIV/SHIV 的猕猴的专业知识 和3（BSL-2、-3）。此外，CNPRC 基础设施和工作人员还提供受感染者的临床分析 动物;这包括物理诊断、微生物分析和血液学评估。兽医 病理学家进行全面的尸检和病理学分析，并为所有人收集组织和器官 本计划中的项目。针对 SIV/猕猴和 RTSHIV/ 的抗逆转录病毒药物的多项研究 猕猴系统，已在 CNPRC 进行；因此，该核心建立在已证明的优势之上 与计划项目的目标直接相关。对于核心 B 的研究，我们假设 SIV/SHIV 感染的猕猴模型可用于定义病毒库、分析潜伏期并 研究病毒在体内的激活。三个具体目标解决了这一假设： 目标 1：定义条件 SIV/猕猴和 RT-SHIV/猕猴系统用于分析病毒潜伏期/病毒库，如在 感染艾滋病毒的人；目标 2：分析接受抗逆转录病毒治疗的受感染猕猴中的病毒定位 治疗;目标 3：确定病毒和宿主细胞因子在病毒潜伏期调节中的作用， 持续性和重新激活。