The prevalence of human immunodeficiency virus (HIV) infection in women of the reproductive age group has been increasing and, with it, vertical transmission of the virus to their infants. The factors that influence the transmission of HIV from mother to baby are not well defined. It is currently believed that intrauterine transplacental infection to the fetus is one important mechanism of vertical transmission, thus a recent focus of investigation has been on the role of the placenta in maternofetal infection. It has been shown that placental macrophages (Hofbauer cells) are susceptible to HIV. The interactions between Hofbauer cells with other cells from the chorionic villi, the regulatory substances secreted and the mechanisms that regulate HIV expression remains to be understood. Since cytokines can regulate HIV expression in T cells and macrophages, the cytokines produced by uninfected and HIV infected Hofbauer cells will be studied and compared to cytokines produced by mixed placenta cell cultures. Supernatants from HIV infected cultures will be assayed for the presence of cytokines known to be associated with suppression of HIV replication, (IFN/alpha/beta and IL-13) and compared with present studies related to stimulatory cytokines (IL-1, TNF, and IL-6). Intracellular expression of the relevant cytokines will be studied following HIV inoculation in vitro as well as the effect of cytokines on HIV expression. Correlation of HIV infection in Hofbauer cells and mixed placenta cell cultures with the type, levels, and expression of cytokines produced and how they influence HIV expression will help in understanding the pathogenesis involved in transplacental transmission of HIV. The present study will be conducted with known lymphocytotropic (HIV-MN) and macrophage-tropic variants (HIV- BaL). Future studies include testing the susceptibility of Hofbauer cells and mixed cultures to HIV variants that are currently being isolated from transmitter and non-transmitter mothers in Puerto Rico in order to identify possible factors that influence transmission.
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