Genetically Defined Herpes/Retrovirus SPF Macaques

这项提议的目标是扩大具有遗传特征的恒河猴的生产 对包括猿猴在内的7种持久性病毒无特定病原体(SPF)的中国血统 免疫缺陷病毒(SIV)、猴D型逆转录病毒(SRV)、猴T淋巴细胞白血病病毒(STLV)、 脑炎疱疹病毒1型(B病毒)、猴泡沫病毒(SFV)、恒河猴巨细胞病毒(RhCMV)和 恒河猴轮状病毒(RRV)。这项拟议的扩大将适用于生产SPF动物以供使用 在艾滋病相关研究方面，并建立一个长期的SPF繁育群体的中国源恒河猴 具有已知的系谱和明确的MHC基因类型的猕猴。为了达到这些目标，我们将 继续通过以下方式从传统的、非SPF的中国恒河猴种群中获得SPF后代 托儿所。-养育新生儿。此外，我们将通过以下途径扩大现有的华裔SPF殖民地 自然繁殖和社会群体中的母亲养育。一个扩展的MHC分型程序，包括 其他微卫星基因座、I类等位基因和II类基因将被用来鉴定后代和他们的 父母。这种扩大的MHC分型将允许识别和定义免疫反应 基因类型，并将允许精选育种产生具有特定遗传特征的动物以响应 以满足研究需求。我们还建议收集与年龄相关的表型和 育苗猕猴和母养SPF猕猴队列中淋巴细胞亚群的功能 在SPF婴儿和非SPF婴儿的队列中，有不同的传染病病原体暴露。年龄- 从正常、健康的SPF猕猴发展而来的特定参考范围，对于更充分地 了解和使用猕猴模型系统，并提供比较数据，以便进行更多 准确解释艾滋病和艾滋病患者淋巴细胞亚群表型和功能改变 其他传染病和免疫性疾病。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类灵长类动物在移植和干细胞研究中的使用 细胞/再生医学。 本申请中提出的工作范围将产生具有良好特征的非人类灵长类动物 用于美国国立卫生研究院资助的艾滋病相关研究的资源。从这里获得的遗传和免疫学数据 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 以及其他传染病。

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.