The central hypothesis of this application is that leukocyte adhesion receptors play crucial roles in a number of aspects of the biology of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), including infectivity, tropism and cytopathicity. The first specific aim of the project is to try to establish in vitro HIV and SIV infectivity assays in which cell-to-cell transmission predominates. Next, the applicant proposes to characterize the role of leukocyte adhesion molecules in transmission of HIV and SIV and to characterize the role of these molecules in induction of HIV expression. The fourth goal of the project is to evaluate the potential contribution of leukocyte adhesion molecules to the tropism of HIV and SIV. The last goal of the applicant is to try to characterize the effect of HIV infection on the expression and function of leukocyte adhesion molecules. The investigator proposes to use monoclonal antibodies and other probes to examine the role of adhesion molecules in virus transmission in the presence of agents such as azidothymidine (AZT) and interferon-alpha which block infection by free virus. He also proposes using vif-defective HIV which infects poorly as free virus but infects in cell-to-cell transmission assays. Leukocyte function assays and Northern blot analysis will be used to study the effect of HIV and SIV infection on expression and function of adhesion molecules.
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