Early events in HIV transmission through a human reconstructed vaginal mucosa

• Published in: AIDS (London) Vol. 22; no. 11; pp. 1257 - 1266
• Main Authors: BOUSCHBACHER, Marielle, BOMSEL, Morgane, VERRONESE, Estelle, GOFFLO, Sandrine, GANOR, Yonatan, DEZUTTER-DAMBUYANT, Colette, VALLADEAU, Jenny
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 11-07-2008
• Subjects: AIDS/HIV; Biological and medical sciences; Cells, Cultured; Epithelial Cells - metabolism; Female; HIV - physiology; HIV Infections - metabolism; HIV Infections - transmission; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Langerhans Cells - metabolism; Langerhans Cells - virology; Medical sciences; Membrane Proteins - metabolism; Models, Anatomic; Mucous Membrane - virology; Tight Junctions - metabolism; Vagina - metabolism; Vagina - virology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Human; Immunopathology; Mucosa; Transmission; Retroviridae; Vagina; AIDS; Immune deficiency; Lentivirus; Infection; Virus; Langerhans cell; Viral disease; Langerhans cells; Human immunodeficiency virus; HIV infection; vaginal mucosa
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/QAD.0b013e3282f736f4

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.
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.
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.
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.