IMMUNOMORPHOLOGIC BASIS FOR SIV PATHOGENECITY

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Since Acquired Immunodeficiency Syndrome (AIDS) was first reported six years ago, the incidence has relentlessly increased. Great advances in the understanding of the molecular biology of human immunodeficiency virus (HIV), the etiologic agent, have occurred during this time period, but the pathogenetic mechanisms leading to the morphologic alterations in various organs (e.g. brain, lymph node, skin, gastrointestinal tract) are largely unknown. Part of this void may be explained by the ethical, practical and epidemiological considerations involved in identifying and studying seropositive individuals who will subsequently develop AIDS. Such work, however, could be facilitated with an animal model for AIDS. Simian immunodeficiency virus (SIV) is a T-cell tropic lentivirus with remarkable parallels to HIV, and it induces a strikingly similar immunodeficiency syndrome in rhesus monkeys. The work outlined in this proposal seeks to 1) identify cellular targets of SIV-infection, 2) study the chronological immunomorphologic changes in lymphoid organs during infection, and 3) correlate these findings with in vitro functional alterations of specific cell phenotypes. The results obtained by this work may provide important insights into the pathogenesis of both SIV- and HIV- related clinical disease.