HUMAN TISSUE MODEL FOR HETEROSEXUAL HIV INFECTION

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During 1998, 75,000 North Americans and Western Europeans became newly infected with human immunodeficiency virus (HIV), the virus that leads to acquired immune deficiency syndrome (AIDS). Worldwide, 6 million new infections occurred during 1998, bringing the total number of people living with HIV/AIDS to 33.4 million. Heterosexual transmission is now responsible for the large majority of new infections worldwide. Although HIV transmission can often be prevented by condom use, there is considerable interest in developing female controlled methods to prevent HIV transmission since reliable, consistent condom use does not always occur. In addition, since the mechanisms of vaginal transmission of HIV are poorly understood a human based model to study HIV infection, transmission, and the prevention thereof would be of great utility in combating the worldwide HIV epidemic. Phase I research will develop an immuno-competent model of normal human vaginal epithelial tissue (HVT). Normal vaginal epithelial (VE) cells will be harvested, expanded in monolayer culture, and cryopreserved. New cell culture methods will be applied to induce VE cells to form a differentiated structure, which mimics in vivo VE tissue and Langerhans cells (LC) will be incorporated therein. The tissue will be characterized in terms of morphology, ultrastructure, and phenotype. Finally, whether HIV will infect the HVT according to mechanisms known to occur in vivo will be investigated. PROPOSED COMMERCIAL APPLICATION: The proposed HVT model will provide the pharmaceutical industry with a reproducible, cost-effective in vitro system to assist in the development of new viricides and microicides aimed at preventing sexurally transmitted diseases (STD), such as HIV. In addition, the human cell based model will avoid species extrapolation and will likely yield new insight into the mechanisms of heterosexual infection/transmission of HIV, and hence suggest novel prophylactic measures of prevention.