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 maturity on controlling viral replication. The limited availability of rhesus macaques (Macaca mulatta) specific pathogen free of B virus (BV), Simian T lymphotropic Virus (STLV-l), 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 biosafety and to reduce confounding variables associated with coinfection 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 conduct of certain research programs. The NERPRC first established a breeding colony free of BV, STLV-1, SRV-D and SW in 1988 and this colony has been instrumental in meeting it's regional 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 fiinded the construction of a $3.IM specific pathogen free rhesus macaque breeding facility. This application proposes to expand and further refine the existing NERPRC colony to take advantage of this and other improvements. To accomplish this goal we propose the following specific aims: l) Specific aim one: To expand the NERPRC rhesus macaque breeding colony specific pathogen free of BV, STLV-l, SRV-D and SIV through internal recruitment, doubling production in the next five years. 2) Specific aim two: To establish """"""""super-clean"""""""" breeding groups free of the target SPF viruses and to five additional viral agents including LCV, RhCMV, RRV, SV40 and SFV. 3) Specific aim three: To enhance MHC typing and genetic testing with the goal of establishing MHC defined breeding groups.
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