Genetics Abstract The CNPRC has maintained a pedigreed colony of Indian-origin rhesus macaques for over 20 years. The SPF Pedigreed Indian origin rhesus colony includes both an SPF level 1 colony negative for Simian Retrovirus (SRV), Simian Immmunodeficiency Virus (SIV) and Simian T Cell Lymphotropic Virus (STLV), Herpes B virus (B virus) and an SPF level 2 colony free of three additional viruses including include rhesus cytomegalovirus (RhCMV), simian foamy virus (SFV), and rhesus rhadinovirus (RRV). All colony animals have had MHC typing for Mamu-A*01, Mamu-A*08, and Mamu-B*01, and the colony is managed to optimize genetic diversity. This proposal will expand the characterization of the Major Histocompatibility Complex (MHC) to include Class I (Mamu-A and -B) and Class II (Mamu-DRB, -DQA, -DQB, -DPA, and -DPB) loci. To genotype these markers, the U42 Genetic Typing Core will submit samples from our adult SPF rhesus macaques to the Genetics Services Unit at the WNPRC. The application proposes to. The four principal goals of this application are: Continue to expand the SPF Level 2 population relative to Level 1 while maintaining overall colony size. Develop improved and expanded screening and confirmatory tests for detecting SPF agents to facilitate the maintenance of the SPF colony. We will initiate annual surveillance for Trypanosoma cruzi in recognition of the expansion of the geographic range of this parasitic infection. This work includes new assays for agents such as tuberculosis, representing the first SPF agent. Maintain genetic analysis to determine the pedigree of Indian rhesus macaques born into the colony and test all adult breeders to characterize their Major Histocompatibility Complex (MHC) Class I (Mamu-A and -B) and Class II (Mamu-DRB, -DQA, -DQB, -DPA, and -DPB) loci. Continue collecting and storing intestinal microbiome and peripheral blood lymphocyte samples in a unique SPF Level 2 biorepository to facilitate future research projects investigating the interaction of HIV with the host microbiome and immune system.