Core - Animal Model

核心-动物模型

基本信息

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
项目类别：
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

项目摘要

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动物研究所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。