Heterosexual transmission of human immunodeficiency virus-1 (HIV-1), from men to women, involves exposure to infectious HIV-1 in semen. Therefore, the cellular and molecular processes that underlie HIV-1 transmission are closely interconnected with fundamental principles of human reproductive biology. Human ex vivo organ culture systems allow experimental reconstruction of HIV-1 transmission, using human semen and premenopausal cervicovaginal mucosal tissue, with specific emphasis on the progression from exposure to development of primary HIV-1 infection. Clearly, an isolated piece of human tissue cannot duplicate the full complexity of events in natural infections, but with correct observation of conventional medical and ethical standards, there is no opportunity to study HIV-1 exposure and primary infection in young women. Human mucosal organ cultures allow direct study of HIV-1 infection in a reproducible format while retaining major elements of complexity and variability that typify community-based HIV-1 transmission. Experimental manipulation of human mucosal tissue both allows and requires acquisition of new insights into basic processes of human mucosal immunology. Expanding from the current foundations, we believe that human organ cultures will become increasingly prominent in experimental studies of HIV-1 transmission and continuing efforts to prevent HIV-1 infection at human mucosal surfaces.
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We thank our colleagues Drs Ashley Haase, Qingsheng Li, Stefan Pambuccian, Stephen Schmechel, Timothy Schacker, and Patrick Schlievert for their interest and constructive discussions during the development of ex vivo organ culture systems at the U of MN and Dr Stephen McSorley for the original suggestion to write this review. We also acknowledge the insight and commitment of a limited number of pioneers who have established the foundations for research with human organ culture systems, some highly active and leading the field today and others who were more active in previous decades. Our work would not be possible without the invaluable assistance of Ms Sarah Bowell in the Tissue Procurement Facility, a component of BioNet within the University of Minnesota Academic Health Center, and many anonymous patients who have allowed tissue samples to be used for research purposes with Institutional Review Board (IRB) approval. This work was supported in part by National Institutes of Health Grant DE 15090.
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