ALCOHOL, SIV INFECTION AND HOST DEFENSE

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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. This projects tests the hypothesis that alcohol functions as a cofactor to accelerate the progression of SIV infection, and to increase host susceptibility to opportunistic infections which, in turn, will further accelerate disease progression. The purposes of current studies are to identify mechanisms by which alcohol impacts SIV disease progression by examining the host defense response to SIV, and to study the effect of pneumonia on SIV expression. Methods: For this, 24 rhesus macaques have had gastric catheters surgically implanted to administer either ethanol or sucrose (control subjects) for the duration of a protocol. Animals were infected with SIVmac251 3 months after starting alcohol and infected with Streptococcus pneumoniae 4 months after SIV inoculation. Blood samples and bronchial alveolar lavage were obtained at selected times. Results/Discussion: Alcohol treatment increased plasmas viral set point. Analysis of SIV-specific CD4+ and CD8+ T cell response and anti-SIV antibody response is ongoing. In response to lung infection, SIV copies recovered in BAL fluid was increased in both sucrose and alcohol treated animals in association with an increase in nuclear NF-kB. The duration of the increase was greater in alcohol compared sucrose animals (14 days vs 1 day). In addition, a careful analysis of animals with prolonged gastric catheters was carried out which allowed us to improve catheter care. These studies indicate that alcohol abuse may accelerate disease progression, in part, by suppressing host defense against the infection and prolonging up regulation of virus production in response to an opportunistic infection. Continued studies with a well-defined and accepted nonhuman primate model of HIV infection will provide novel and important information on the effects of alcohol on HIV disease transmission, pathogenesis, progression and treatment.