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. Alcohol abuse and human immunodeficiency virus (HIV) infection are common and frequently coexist in the same individual. Alcohol consumption has long been known to suppress critical aspects of both innate and specific immunity thereby increasing host susceptibility to infections. HIV infection primarily exerts its pathogenic effects on immune cells expressing CD4 membrane receptor which leads to progressive depletion of the CD4+cells, compromised immunosurveillance, opportunistic infections, and death. Currently, there is little information on how these two immunosuppressive states interact to alter host defense mechanisms directed against both the primary viral infection and/or secondary opportunistic infections. The focus of this project is to determine the impact of alcohol on the progression and sequelae of SIV infection in rhesus monkeys as it relates to the primary infection itself and the development of secondary infections. It is our hypothesis that alcohol functions as a cofactor to accelerate the progression of SIV infection as well as to increase host susceptibility to opportunistic infections which, in turn, will further accelerate progression of SIV infection. This research tests this hypothesis by addressing 3 Specific Aims: 1) To determine the effect of alcohol consumption on primary infection with SIV, progression of SIV infection, and the subsequent development of opportunistic infections. 2) To examine in vivo the separate and combined effects of alcohol consumption and SIV infection on the innate immune system of the lung. 3) To determine the in vivo effect of alcohol consumption on indices of SIV disease progression in response to experimental intrapulmonary infection. Addressing these specific aims in the context of a well-defined and accepted nonhuman primate model of HIV infection will provide novel and important information on the effects of alcohol on altering host defenses to both primary infection with HIV and its progression.