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

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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.