title: New approaches to making the microenvironment of the female reproductive tract hostile to HIV.
abstract: The studies presented in this review explore three distinct areas with potential for inhibiting HIV infection in women. Based on emerging information from the physiology, endocrinology and immunology of the female reproductive tract (FRT), we propose unique 'works in progress' for protecting women from HIV. Various aspects of FRT immunity are suppressed by estradiol during the menstrual cycle, making women more susceptible to HIV infection. By engineering commensal Lactobacillus to secrete the anti-HIV molecule Elafin as estradiol levels increase, women could be protected from HIV infection. Selective estrogen response modifiers enhance barrier integrity and enhance secretion of protective anti-HIV molecules. Finally, understanding the interactions and regulation of FRT endogenous antimicrobials, proteases, antiproteases, etc., all of which are under hormonal control, will open new avenues to therapeutic manipulation of the FRT mucosal microenvironment. By seeking new alternatives to preventing HIV infection in women, we may finally disrupt the HIV pandemic.
authors.affiliation: Department of Physiology and Neurobiology, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH 03756, USA. John.V.Fahey@Dartmouth.edu
authors.forename: John V
authors.initials: JV
authors.lastname: Fahey
authors.forename: Jack E
authors.initials: JE
authors.lastname: Bodwell
authors.forename: Danica K
authors.initials: DK
authors.lastname: Hickey
authors.forename: Mimi
authors.initials: M
authors.lastname: Ghosh
authors.forename: Maria N
authors.initials: MN
authors.lastname: Muia
authors.forename: Charles R
authors.initials: CR
authors.lastname: Wira
mesh_terms: D019380:Anti-HIV Agents / Q000378:metabolism; D018407:Bacterial Physiological Phenomena; D053492:Elafin / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000009:adverse effects / Q000097:blood*; D005260:Female; D005836:Genitalia, Female / Q000276:immunology / Q000382:microbiology / Q000502:physiology* / Q000821:virology*; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007778:Lactobacillus / Q000235:genetics; D009092:Mucous Membrane / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D053492:Elafin; D020845:Selective Estrogen Receptor Modulators; D004958:Estradiol