The goal of this proposal is to expand the production of genetically characterized rhesus macaques of Indian-ancestry that are specific pathogen-free (SPF)for an expanded list of 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 Indian-origin rhesus macaques with known pedigrees and well-defined MHC genotypes. To meet these objectives, we will derive SPF offspring from conventional, non-SPF Indian rhesus breeding stock through nursery.-rearing of neonates. In addition, we will expand the existing Indian-origin colony that is SPF for 5 persistent viruses (SIV, SRV, STLV, SFV,B virus) 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. We also propose to collect longitudinal data on age-related changes in the major lymphocyte subsets in cohorts of nursery-reared and mother-reared SPF rhesus macaques. 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 alterations observed in AIDS and other infectious and immunologic diseases. The rhesus monkeys produced as part of this grant will provide valuable resources for AIDS-related research. These animals will be used for research related to vaccine development and anti-viral therapy.
