GENETICALLY DEFINED HERPES/RETROVIRUS SPF MACAQUES: AIDS: THERAPEUTIC AGENT DVMT

基因定义的疱疹/逆转录病毒 SPF 猕猴：艾滋病：治疗剂 DVMT

• 批准号: 8173365
• 负责人: NICHOLAS WILLIAM LERCHE
• 金额: $ 34.08万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173365
• 关键词: Acquired Immunodeficiency Syndrome; Address; Alleles; Animals; Antibodies; Biological Assay; Breeding; Cercopithecine Herpesvirus 1; Chinese People; Computer Retrieval of Information on Scientific Projects Database; Cytomegalovirus; Data; Detection; Development; Frequencies; Funding; Genotype; Goals; Grant; Haplotypes; Herpesviridae; Immune response; In Vitro; Institution; MHC Class II Genes; Macaca; Macaca mulatta; Major Histocompatibility Complex; Methods; Microsatellite Repeats; Natural History; Polymerase Chain Reaction; Production; Research; Research Personnel; Resources; Retroviridae; Rhadinovirus; SIV; Screening procedure; Simian Foamy Virus; Simian T-lymphotropic virus 1; Source; Specific Pathogen Frees; System; Therapeutic Agents; Type D Retrovirus; United States National Institutes of Health; Viral; Viral Antigens; Virus; Virus Shedding; cell mediated immune response; cost; cost effectiveness; genetic pedigree; genetic profiling; germ free condition; high throughput screening; meetings; offspring; pathogen; programs; response; sound

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. DESCRIPTION (Provided by applicant): The goal of this project is to expand the production of genetically characterized rhesus macaques that are specific pathogen free (SPF) for an extended list of persistent viruses, including simian immunodeficiency virus (SIV), simian T-lymphotropic virus (STLV-1), simian type D retrovirus (SRV-D), simian foamy virus (SFV), Cercopithecine herpesvirus I (B virus), rhesus cytomegalovirus (RhCMV), and rhesus rhadinovirus (RRV). This expansion will be geared to the production of SPF animals for use in AIDS-related and other NIH-funded research, and to establishing a long-term SPF breeding colony of rhesus macaques with known pedigrees and well-defined major histocompatability complex (MHC) genotypes. To meet these objectives, the investigators will derive SPF offspring from conventional non-SPF rhesus breeding stock of Chinese origin. An expanded program of MHC typing will be used to characterize breeding stock and offspring that will include additional microsatellite loci, class I alleles and class II genes. This expanded MHC typing will facilitate the identification and definition of immune response genotypes, and will allow for selected breeding to produce animals with specific genetic profiles in response to shifting research needs. Data generated by these studies will also allow the investigators to determine whether significant differences in MHC haplotype frequencies (which could reflect differences in immune response) exist between Chinese origin and Indian origin rhesus macaques. The determination and confirmation of B virus status has proven to be one of the most problematic aspects of SPF colony development. Augmented B virus screening utilizing polymerase chain reaction detection of viral shedding and in vitro assessment of cell-mediated immune responses to B virus antigens will be implemented for B virus surveillance. These studies will provide information on aspects of the natural history of B virus critical to the sound management and continued integrity of SPF macaque colonies. As the number of animals involved in SPF programs increases and the list of specific pathogens expands, there is a need for increased efficiency and cost-effectiveness of methods used for large-scale screening. To address this need, the investigators will optimize and validate a multiplex system for sero-detection of antibodies to multiple viral agents in a single assay. This multiplex system will allow for high throughput screening at reduced cost and will be used in support of the SPF colony development.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 DESCRIPTION (Provided by applicant): The goal of this project is to expand the production of genetically characterized rhesus macaques that are specific pathogen free (SPF) for an extended list of persistent viruses, including simian immunodeficiency virus (SIV), simian T-lymphotropic virus (STLV-1), simian type D retrovirus (SRV-D), simian foamy virus (SFV), Cercopithecine疱疹病毒I（B病毒），恒河猴（RHCMV）和恒河猴rhadinovirus（RRV）。 这种扩展将用于生产SPF动物，用于用于与艾滋病有关的和其他NIH资助的研究，并建立具有恒河猕猴的长期SPF繁殖菌落，并具有已知的谱系和明确定义的主要组织能力复合物（MHC）基因型。 为了实现这些目标，调查人员将从中国起源的常规非SPF恒河猴繁殖中得出SPF后代。 扩展的MHC键入程序将用于表征繁殖量和后代，其中包括其他微卫星基因座，I类等位基因和II类基因。 这种扩展的MHC键入将促进免疫反应基因型的鉴定和定义，并允许选定的育种生产具有特定遗传特征的动物，以响应转移的研究需求。 这些研究产生的数据还将允许研究人员确定中国与印度恒河猕猴之间是否存在MHC单倍型频率的显着差异（可能反映了免疫反应的差异）。 事实证明，B病毒状况的确定和确认是SPF菌落开发中最有问题的方面之一。 利用聚合酶链反应检测病毒脱落的反应检测以及对细胞介导的对B病毒抗原的免疫反应的体外评估的增强B病毒筛查将用于B病毒监测。 这些研究将提供有关B病毒自然史的各个方面对SPF猕猴菌落的持续完整性至关重要的。随着SPF计划中涉及的动物的数量增加，特定病原体的列表随着用于大规模筛查的方法的效率和成本效益而需要提高。 为了满足这一需求，研究人员将优化和验证多重系统，以在单个测定中对多种病毒剂的抗体进行血清检测。 该多重系统将允许以降低成本进行高吞吐量筛查，并将用于支持SPF菌落开发。