The objectives of the proposed research are to investigate whether antibodies specific for HIV envelope protein potentiate HIV infection and whether those antibodies that do not neutralize HIV infectivity do more harm than good in the immunity against HIV. The results of the studies will bear significant implications in the development of vaccines against AIDS. Recent studies have indicated that macrophage is possibly an important site for the replication of HIV in infected individuals. Some macrophages express on their surface low densities of CD4 antigen which presumably reacts with envelope protein of HIV and serves as a receptor molecule for the entry of HIV into macrophages. Macrophages are also known to express receptors for Fc portions of antibodies (FcR) and receptors for the third component of the complement (CR3). After antibodies against HIV are induced, the antibodies bind to HIV. Consequently, FcR and CR3 molecules may become sites for HIV to attach to indirectly and enter macrophages.
The specific aims to be accomplished in the 3 year project period are: (1) to establish sensitive ELISAs to quantitate HIV antigens in macrophages and nucleic hybridization assay to quantitate HIV-specific RNA in macrophages, (2) to study the effects of HIV envelope protein-specific polyclonal antibodies and monoclonal antibodies of different isotypes and subclasses on the uptake of HIV by macrophages and its replication in the cells, (3) to use anti-CD4a, anti-CR3, and other monoclonal antibodies to study the relative importance of CD4, FcR and CR3 as the macrophage surface receptor sites for HIV, and (4) to study the relative preference of T helper cells and macrophages as targets of HIV in the absence and presence of antibodies.
