ALCOHOL, SIV INFECTION AND HOST DEFENSE

这个子项目是众多研究子项目之一

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: 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, and HIV primarily exerts its pathogenic effects by infecting and depleting CD4 T lymphocytes. However, how alcohol impacts HIV disease transmission, pathogenesis, progression and treatment are poorly understood. This projects tests the 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 by addressing the following Specific Aims: 1) to test the hypothesis that alcohol increases the plasma viral set point in SIV infected macaques by compromising viral specific T lymphocyte responses; 2) to test the hypothesis that upregulation of SIV replication during pneumococcal pneumonia is enhanced by alcohol consumption; 3) to test the hypothesis that this increase in SIV replication in the lung is induced by activation of NF-kB in alveolar macrophages; and 4) to test the hypothesis that this increased of SIV proliferation in the lung results in the generation of new SIV genotypes that are associated with increased disease progression. Methods: Currently, 25 rhesus macaques have surgically implanted catheters used to administer either ethanol or sucrose (control subjects) solution after infection with SIV. All animals are examined under anesthesia once weekly and samples are collected at that time. Results: Preliminary data reveals that alcohol does not alter the CD8+ specific in response to SIV infection. However, ongoing studies show that alcohol may increase SIV presence in bronchoalveolar lavage fluid (BALF) 4 months PI, and increases SIV production in lungs challenge with pneumococcus by in part increasing nuclear NF-kB. Conclusion: Completing 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.