Early events in HIV transmission through a human reconstructed vaginal mucosa

Bouschbacher, Mariellea; Bomsel, Morganeb; Verronèse, Estellea; Gofflo, Sandrinea; Ganor, Yonatanb; Dezutter-Dambuyant, Colettea; Valladeau, Jennya

AIDS:
doi: 10.1097/QAD.0b013e3282f736f4
Basic Science
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.

Conclusion: 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.

Author Information

From the aClaude Bernard Lyon 1 University, Centre Hospitalier Edouard Herriot, Lyon, France

bCochin Institute, INSERM U567, CNRS-UMR 8104, Université Descartes-IFR 116, Paris, France.

Received 28 June, 2007

Revised 12 December, 2007

Accepted 18 December, 2007

Correspondence to Jenny Valladeau, INSERM U590, Centre Léon Bérard, 28 rue Laennec, 69473 Lyon cedex 08, France. E-mail: valladea@lyon.fnclcc.fr

© 2008 Lippincott Williams & Wilkins, Inc.