The SIV-infected rhesus macaque has emerged as the premiere animal model of human AIDS and has lead to important advances in understanding aspects of disease pathogenesis, the role of viral determinants on disease progression and the impact of host immunity in controlling viral replication. The limited availability of Indian-origin rhesus macaques (Macaca mulatta) specific pathogen free of B virus (BV), Simian T lymphotropic Virus (STLV-1), Simian Retrovirus Type D (SRV-D) and Simian Immunodeficiency Virus (SIV) has become an impediment to investigators conducting animal model based AIDS-related research. Such animals are important for reasons of colony health, and biosafety and to reduce confounding variables associated with co-infection with these viruses. In addition to these requirements, animals free of other infectious agents or of defined MHC type have become increasingly important in the implementation of certain research programs. The NEPRC first established a breeding colony free of BV, STLV-1, SRV-D and SIV in 1988 and this colony has been instrumental in meeting its national resource mission by providing well-defined animals to core and collaborating scientists for use in AIDS-related research. In recognition of the importance of this colony, Harvard University recently funded the construction of a $3.1 M specific pathogen free rhesus macaque breeding facility and a $7.1M SPF macaque housing and testing facility. This application proposes to expand and further refine the existing NEPRC colony to take advantage of these and other improvements. To accomplish this goal we propose the following specific aims: 1) To expand the NEPRC breeding colony specific pathogen free of BV, STLV-1, SRV-D and SIV through internal and external recruitment of well-defined Indian-origin rhesus macaques;2) To continue virologic testing of the SPF colony and expand microbiologic assessment of the SPF and """"""""super-clean"""""""" breeding groups;and 3) To continue MHC typing and genetic testing with the goal of enhancing colony management and the biological resource.
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