This proposal is directed to the molecular pathogenesis of infection by the human immunodeficiency virus (HIV) and in particular to the basis for its cardinal manifestation, the acquired immuno deficiency syndrome (AIDS). We describe longitudinal analyses of lymph node and bone marrow by in situ hybridization and cognate single cells methods to define the number and type of cells which harbor HIV, and the extent of virus gene expression vis-a-vis viral and regulatory genes and stage of disease. We think this analysis will provide support for a war of attrition hypothesis which accounts for the profound loss of T helper lymphocytes despite the relatively low frequency of cells in which viral RNA can be demonstrated. We also will look for a mutant virulent virus in the later stages of disease. If one is found we will characterize the genome of the virus for comparisons with earlier isolates with the aim of identifying viral genes with a critical role in pathogenesis.
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