title: Early events in HIV transmission through a human reconstructed vaginal mucosa.
abstract: OBJECTIVE
  The early steps of HIV entry into intact vaginal mucosa still need to be clarified. Here we investigated how HIV translocated across the vaginal pluristratified epithelium, either by transcytosis or by uptake in Langerhans cells.
  
  
  METHODS
  Using human primary fibroblasts and vaginal epithelial cells, we developed an in-vitro model of vaginal mucosa in which Langerhans cells could also be integrated. Owing to the absence of T lymphocytes and macrophages, we specifically studied the role of Langerhans cells in HIV transmission and the transcytosis of cell-associated HIV.
  
  
  RESULTS
  Our model has a normal mucosal tissue architecture and Langerhans cells were efficiently integrated within the pluristratified epithelium. In addition, tight junction proteins' expression, high transepithelium resistance and low fluorescein isothiocyanate-BSA passage confirmed the integrity and impermeability of the reconstruction. Furthermore, we showed that human Langerhans cells also expressed tight junction proteins. Then, we demonstrated that neither transcellular nor intercellular transport of free infectious virus released by R5-infected or X4-infected peripheral blood mononuclear cells inoculated apically occured in the vaginal mucosa, irrespective to the presence of Langerhans cells.
  
  
  CONCLUSIONS
  For the first time, we documented that, within 4 h following contact with HIV-infected cells, translocation of free HIV particles across a pluristratified mucosa is not detectable and that, in this context, it seemed that Langerhans cells do not increase HIV transmission. Moreover, we provided a useful model for the development of strategies preventing HIV entry into the female genital tract, especially for testing the efficiency of various microbicides.
authors.affiliation: Claude Bernard Lyon 1 University, Centre Hospitalier Edouard Herriot, Lyon, France.
authors.forename: Marielle
authors.initials: M
authors.lastname: Bouschbacher
authors.forename: Morgane
authors.initials: M
authors.lastname: Bomsel
authors.forename: Estelle
authors.initials: E
authors.lastname: Verronèse
authors.forename: Sandrine
authors.initials: S
authors.lastname: Gofflo
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Ganor
authors.forename: Colette
authors.initials: C
authors.lastname: Dezutter-Dambuyant
authors.forename: Jenny
authors.initials: J
authors.lastname: Valladeau
mesh_terms: D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006678:HIV / Q000502:physiology*; D015658:HIV Infections / Q000378:metabolism / Q000635:transmission*; D006801:Humans; D007801:Langerhans Cells / Q000378:metabolism / Q000821:virology; D008565:Membrane Proteins / Q000378:metabolism; D008953:Models, Anatomic; D009092:Mucous Membrane / Q000821:virology; D019108:Tight Junctions / Q000378:metabolism; D014621:Vagina / Q000378:metabolism / Q000821:virology*
chemical_list: D008565:Membrane Proteins