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A topical microbicide reduces the probability of virus transmission when applied to the vagina or rectum of a person at risk of sexually acquiring HIV-1 infection. An effective microbicide could significantly reduce the global spread of HIV-1, particularly if women were able to use it covertly to protect themselves. A microbicide could target the incoming(More)
P-glycoprotein (MDR-1) is a well-known transporter that mediates efflux of chemotherapeutic agents from the intracellular milieu and thereby contributes to drug resistance. MDR-1 also is expressed by nonmalignant cells, including leukocytes, but physiologic functions for MDR-1 are poorly defined. Using an initial screening assay that included >100 mAbs, we(More)
Dendritic cells (DCs) are a distinct lineage of white cells that arise from CD34+ progenitors in the bone marrow. DCs exhibit many specializations that lead to efficient antigen capture and presentation to T cells, both CD4+ helpers and CD8+ killers. In several human tissues, DCs express the CD4 receptor for HIV-1. Some early reports described the explosive(More)
Experimentally, a productive infection with HIV-1 requires that virus be administered to T cells that are activated by mitogens. We describe a productive milieu for HIV-1 within the confines of normal skin that does not require standard stimuli. The milieu consists of dendritic cells and T cells that emigrate from skin and produce distinctive stable,(More)
Identification of cellular factors involved in HIV-1 entry and transmission at mucosal surfaces is critical for understanding viral pathogenesis and development of effective prevention strategies. Here we describe the evaluation of HIV-1 entry inhibitors for their ability to prevent infection of, and dissemination from, human cervical tissue ex vivo.(More)
The early events during infection with an immunodeficiency virus were followed by application of pathogenic simian immunodeficiency virus atraumatically to the tonsils of macaques. Analyses by virologic assays and in situ hybridization revealed that the infection started locally in the tonsils, a mucosal-associated lymphoid organ, and quickly spread to(More)
A procedure has been developed to isolate dendritic cells to a high degree of purity from fresh blood. Prior enrichment methods have relied upon an initial 1-2-d culture period. Purified fresh isolates lack the characteristic morphology, phenotype, and immunostimulatory function of dendritic cells. The purified cells have the appearance of medium sized(More)
HIV-1 subverts antigen processing in dendritic cells (DCs) resulting in viral uptake, infection, and transfer to T cells. Although DCs bound monomeric gp120 and HIV-1 similarly, virus rarely colocalized with endolysosomal markers, unlike gp120, suggesting HIV-1 alters endolysosomal trafficking. Virus within DC intracellular compartments rapidly moved to(More)