Alcohol consumption and HIV infection are frequently co-existent pathologies. Muscle wasting is a common feature of both conditions. The alterations in immune responses resulting from chronic alcohol consumption have been hypothesized to enhance the transmission and acquisition of HIV or the progression from HIV infection to acquired immunodeficiency syndrome (AIDS). Based on available information, it is possible to speculate that these are either related to the direct effects of alcohol on the immune system, or are secondary to the impact of alcohol consumption on the nutritional state of the individual. Excess alcohol consumption is associated with a approximately 50% incidence of skeletal muscle myopathy. Alcohol consumption impairs the nutritional state of the individual either as a result of decreased food consumption or as a result of decreased absorption. affecting micronutrients which in turn have been shown to modulate circulating and tissue levels of growth factors. Hence the effects of alcohol consumption on muscle wasting appear to be multifactorial. Alcohol-induced myopathy appears to be predominantly the result of decreases in muscle protein synthesis, and is characterized by decreased weight, protein, RNA and DNA contents in skeletal muscle. The general hypothesis of the present proposal is that alcohol consumption accelerates and worsens the muscle wasting associated with HIV infection, leading to increased morbidity and mortality. Infection of Rhesus monkeys with simian immunodeficiency virus (SIV) has been established as an excellent model system for studying the pathogenesis of HIV-like infection. The disease is characterized by diarrhea, weight loss, lymphopenia, thrombocytopenia, and lymphadenopathy/lymphoid hyperplasia progressing to immunosuppression with marked reduction in CD4+ cells and in the CD4+/CD8+ cell ratio, and opportunistic infections.
The aim of the present proposal is to characterize the time-course and relative contribution of alterations in muscle protein synthesis and proteolysis to the progression of muscle wasting associated with chronic alcohol consumption and SIV infection individually and combined. These studies will allow for the longitudinal investigation of the progression of the alterations in muscle metabolism beginning with a healthy, non-infected animal, throughout the acute infectious period and throughout progression to full blown AIDS. These will provide the preliminary data for a more mechanistic approach to the study of the etiology of alcohol-induced muscle wasting and its impact on a chronic infection.
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