Genetically Defined Herpes/Retrovirus SPF Macaques

这项建议的目标是扩大生产的遗传特征的恒河猴， 中国血统，对7种持久性病毒（包括猿猴病毒）无特异性病原体（SPF） 免疫缺陷病毒（SIV），猿猴D型逆转录病毒（SRV），猿猴嗜T淋巴细胞病毒（STLV）， 猴疱疹病毒1（B病毒）、猿猴泡沫病毒（SFV）、恒河猴巨细胞病毒（RhCMV）和 恒河猴脊膜病毒（RRV）。这一拟议的扩张将适合于生产SPF动物供使用 在艾滋病相关研究中的应用，以及建立中国恒河猴SPF长期繁殖群 具有已知谱系和明确的MHC基因型的猕猴。为达致这些目标，我们会 继续从传统的、非SPF的中国恒河猴种源中培育SPF后代， 托儿所。-养育新生儿。此外，我们会透过以下措施， 自然繁殖和社会群体中的母亲养育。MHC分型的扩展程序，包括 额外的微卫星基因座、I类等位基因和II类基因将用于表征后代及其 父母这种扩展的MHC分型将允许识别和定义免疫应答 基因型，并将允许选择育种，以产生具有特定遗传特征的动物， 研究需求。我们还建议收集与年龄相关的表型变化的纵向数据， 在托儿所饲养和母亲饲养的SPF恒河猴队列中淋巴细胞亚群的功能， SPF婴儿和非SPF婴儿队列中感染性疾病病原体的暴露差异。年龄- 从正常、健康的SPF恒河猴开发的特定参考范围对于更全面地 理解和利用猕猴模型系统，并提供比较数据， 准确解释艾滋病中观察到的淋巴细胞亚群表型和功能改变， 其他传染性和免疫性疾病。关于SPF猕猴免疫遗传学的信息将 也影响了这种有价值的非人灵长类动物在移植和干细胞研究中的应用 细胞/再生医学 本申请中提出的工作范围将产生良好表征的非人灵长类动物 用于NIH资助的艾滋病相关研究的资源。遗传学和免疫学数据从这个 该项目将更好地定义和描述恒河猴模型系统，以支持艾滋病研究 和其他传染病。

The goal of this proposal is to expand the production of genetically characterized rhesus macaques of Chinese-ancestry that are specific pathogen-free (SPF) for 7 persistent viruses, including simian immunodeficiency virus (SIV), simian type D retrovirus (SRV), simian T-lymphotropic virus (STLV), Cercopithecine herpesvirus 1 (B virus), simian foamy virus (SFV), rhesus cytomegalovirus (RhCMV) and rhesus rhadinovirus (RRV). This proposed expansion will be geared to the production of SPF animals for use in AIDS-related research, and to establishing a long-term SPF breeding colony of Chinese-origin rhesus macaques with known pedigrees and well-defined MHC genotypes. To meet these objectives, we will continue to derive SPF offspring from conventional, non-SPF Chinese rhesus breeding stock through nursery.-rearing of neonates. In addition, we will expand the existing Chinese-origin SPF colony through natural breeding and mother-rearing in social groups. An expanded program of MHC typing that includes additional microsatellite loci, class I alleles, and class II genes will be used to characterize offspring and their parents. This expanded MHC typing will allow the identification and definition of immune response genotypes, and will allow for selected breeding to produce animals with specific genetic profiles to respond to research needs. We also propose to collect longitudinal data on age-related changes in phenotype and function of lymphocyte subsets in cohorts of nursery-reared and mother-reared SPF rhesus macaques and in cohorts of SPF infants and non-SPF infants with differential exposure to infectious disease agents. Age- specific reference ranges, developed from normal, healthy SPF-rhesus macaques, are essential to more fully understand and utilize the macaque model system, and to provide comparative data allowing for more accurate interpretation of lymphocyte subset phenotype and functional alterations observed in AIDS and other infectious and immunologic diseases. Information on the genetics of immunity in SPF macaques will also impact the use of this valuable nonhuman primate for research on transplantation and stem cell/regenerative medicine. The scope of work proposed in this application will produce well characterized nonhuman primate animal resources for use in NIH-funded AIDS-related research. Genetic and immunologic data obtained from this project will better define and characterize the rhesus macaque model system in support of research on AIDS and other infectious diseases.