Our broad long-term objective is to prevent sexual transmission of HIV by changing the genital tract milieu to one that decreases the risk of HIV infection. Since a major route of HIV transmission is between heterosexual partners, a promising HIV-prevention approach is to topically modify the microbiology and immunology of the female genital tract. Using our recently published cervical explant model, we intent to investigate the role of cervical secretion (CVL)s in determining the susceptibility to HIV-1 infection. Our laboratory is particularly well- qualified to investigate key HIV-1 related modifications in the immunology and virology of the female genital tract including susceptibility to HIV infection and expression on HIV-receptors such as chemokine receptors (CheRec) and CDR. Our hypothesis is: HIV-1 susceptibility is altered by the microbiology/immunology of the female genital tract through the production of factors in cervical secretion (CVL)s that either inhibit or stimulate HIV-1 production. In the following AIMS, we propose 4 questions corresponding to 2 different intentionally in explant culture. [1a] Does the addition of lysates from cultures of organisms known to cause bacterial vaginosis (see subproject 0001, a condition associated with increased risk of HIV-1 transmission, to cut our cervical explant model increase or decrease susceptibility to different isolates of HIV-1? [1b] Does the addition of cervical [CVL)s from women in our cohorts with cultured confirmed bacterial vaginosis to our cervical explant model increase or decrease susceptibility to different isolates of HIV-1? [2a] Does the addition of IgA or IgG from cervical secretions (CVL)s of HIV-1 exposed-uninfected women (see subproject 0002) to our cervical explant model increase or decrease susceptibility to different isolates of HIV-1? (2b) Does the addition of cervical secretion (CVLs)s (i.e. IgA), known to inhibit HIV-1 in vitro, from HIV-1, exposed-uninfected women (see subproject 0001) to our cervical explant model increase or decrease susceptibility to different isolates of HIV-1? Confirmation of our hypotheses of our hypotheses through these specific aims may result in successful HIV-1 prevention strategies applicable to women in developing nations.
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