This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: Our objective is to understand the interaction, function and regulation of human immunodeficiency virus type 1 (HIV-1) and the human immune system using the monkey model. This model had been used for over two decades to understand pathogenesis and immune functions of HIV-1 infection of humans. As a result of this work, potent anti-viral drugs, immune enhancing proteins, entry inhibiting drugs and microbicides were discovered. Despite of these discoveries and gained knowledge, HIV-1 still rages on devastating many communities around the world. Therefore there is an urgent need to develop safe vaccines;topical barriers and microbicides that can efficiently reduce sexually transmitted HIV-1 infection. Methods: We will continue to utilize this valuable resource for potential discovery of potent anti-viral drugs, immune enhancing proteins, entry inhibiting drugs and microbicides. Results/Discussion: In vitro, using rhesus macaque tissues, we will continue to advance our understanding of pathogenesis in relation to the immune system. Furthermore, we will continue to test new promising anti-HIV-1 blockers, immune modulators and microbicides.