Genetically Defined Herpes/Retrovirus SPF Macaques

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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.