This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Transmission of HIV during breastfeeding remains the most significant challenge for the prevention of mother-to-child HIV transmission (MTCT) worldwide. Although short-course antiretroviral regimens can reduce transmission to as low as 2-4% during the antenatal and intrapartum periods, these gains may be lost during breastfeeding. Both cell-free and cell-associated virus in breast milk is associated with MTCT. Maternal highly active antiretroviral therapy (HAART) reduces the cell-free source of virus in breast milk, but does not lower cell-associated virus. The broad objective of our current studies is to elucidate the mechanisms by which the mammary gland and breast milk serve as a reservoir for persistence of HIV infection and replication in between infant feedings.Our efforts include investigating the role of cytokines and chemokines secreted from milk-producing cells, also known as mammary epithelial cells (MEC), in inducing recruitment, proliferation, and HIV replication in CD4+ target cells. Our preliminary 27-plex Luminex data showed that IL-8 is highly expressed by both the apical and basolateral surfaces of primary human MEC. With the use of immunomagnetic beads against BerEP4, we isolated and cultured primary MEC on transwell inserts until a tightly polarized epithelial monolayer was achieved. MEC-conditioned media from both the apical and basolateral chambers was utilized in experiments to measure IL-8 concentrations. Our recent data indicates that MEC apically-conditioned media significantly increases both the proliferation of, and HIV replication in, CD4+ T lymphocytes. However, neither apically nor basolaterally conditioned media contributes to lymphocyte recruitment. The studies described in this abstract constitute a portion of the preliminary data that were used in conjunction with the application for our recently-funded NIH K08 grant.
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