GENETICALLY DEFINED HERPES/RETROVIRUS SPF MACAQUES: AIDS: ANIMAL MODEL

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 描述（申请人提供）：该项目的目标是扩大具有遗传特征的恒河猴的生产，这些恒河猴对一系列持久性病毒无特异性病原体（SPF），包括猿猴免疫缺陷病毒（SIV）、猿猴嗜T淋巴细胞病毒（STLV-1）、猿猴D型逆转录病毒（SRV-D）、猿猴泡沫病毒（SFV）、猕猴疱疹病毒I（B病毒）、恒河猴巨细胞病毒（RhCMV）和恒河猴腺病毒（RRV）。 这一扩展将适合于生产SPF动物用于艾滋病相关和其他NIH资助的研究，并建立一个长期的SPF猕猴繁殖群体与已知的谱系和明确的主要组织相容性复合体（MHC）基因型。 为了实现这些目标，研究者将从传统的中国非SPF恒河猴种猪中获得SPF后代。 MHC分型的扩展程序将用于表征育种股票和后代，将包括额外的微卫星位点，I类等位基因和II类基因。 这种扩展的MHC分型将有助于识别和定义免疫反应基因型，并允许选择育种以产生具有特定遗传特征的动物，以应对不断变化的研究需求。 这些研究产生的数据还将使研究人员能够确定中国起源和印度起源恒河猴之间是否存在MHC单倍型频率的显著差异（这可能反映免疫应答的差异）。 B病毒状态的确定和确认已被证明是SPF菌落发育中最有问题的方面之一。 将利用聚合酶链反应检测病毒脱落和体外评估细胞介导的对B病毒抗原的免疫应答来加强B病毒筛查，以进行B病毒监测。 这些研究将提供有关B病毒自然史方面的信息，这些信息对SPF猕猴群体的健全管理和持续完整性至关重要。随着参与SPF计划的动物数量的增加和特定病原体清单的扩大，需要提高用于大规模筛查的方法的效率和成本效益。 为了满足这一需求，研究人员将优化和验证一种多重系统，用于在一次检测中对多种病毒因子的抗体进行血清检测。 这种多重系统将允许以降低的成本进行高通量筛选，并将用于支持SPF菌落的开发。

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.