HIV-1 Infection of Langerhans Cells in a Reconstructed Vaginal Mucosa

• Published in: The Journal of infectious diseases Vol. 190; no. 2; pp. 227 - 235
• Main Authors: Sivard, Peggy, Berlier, Willy, Picard, Bertrand, Sabido, Odile, Genin, Christian, Misery, Laurent
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University Chicago Press 15.07.2004; University of Chicago Press; Oxford University Press
• Subjects: Anti-HIV Agents - pharmacology; Antigens, CD34 - analysis; Antiviral Agents - pharmacology; Biological and medical sciences; Chemokine CCL5 - pharmacology; Chemokine CXCL12; Chemokines, CXC - pharmacology; Coculture Techniques; Culture Techniques; Dendritic cells; DNA, Viral - isolation & purification; Epithelial cells; Epithelium; Female; Fundamental and applied biological sciences. Psychology; Hematopoietic Stem Cells - cytology; HIV; HIV 1; HIV-1 - drug effects; HIV-1 - growth & development; HIV-1 - isolation & purification; HIV/AIDS; Human immunodeficiency virus 1; Human viral diseases; Humans; Infections; Infectious diseases; Islets of Langerhans; Langerhans cells; Langerhans Cells - metabolism; Langerhans Cells - virology; Leukocytes, Mononuclear - virology; Medical sciences; Microbiology; Miscellaneous; Mucous Membrane; Proviruses - isolation & purification; Receptors, CCR5 - metabolism; Receptors, CXCR4 - metabolism; Receptors, HIV - metabolism; T lymphocytes; Vagina - cytology; Vagina - metabolism; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virology; Viruses; Zidovudine - pharmacology; Immunopathology; Microbiology; HIV-1 virus; Mucosa; Retroviridae; Vagina; AIDS; Immune deficiency; Lentivirus; Virus; Infection; Langerhans cell; Viral disease; Human immunodeficiency virus
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/421704

We have developed an in vitro reconstructed vaginal mucosa integrating Langerhans cells (LCs), obtained by differentiation of umbilical cord blood CD34+ hematopoietic progenitor cells, and, in this model, we have investigated the infection of LCs by human immunodeficiency virus type 1 (HIV-1). Proviral DNA of X4 (LAI and NL4-3) and R5 (Ba-L) HIV-1 strains were detected in LCs integrated in the reconstituted mucosa. Infection of LCs could be specifically inhibited by the chemokines stromal cell-derived factor 1 (SDF-1) and RANTES (regulated on activation, normally T cell-expressed and -secreted), confirming the presence of functional coreceptors on LCs generated in vitro. A complete inhibition of LCs, by use of a zidothymidine, a reverse transcriptase inhibitor, was also observed. Moreover, HIV-1-infected LCs of the reconstructed mucosa wereable to transmit R5 or X4 HIV-1 strains to activated peripheral blood mononuclear cells. Such a model couldbe a useful tool to study the mechanisms involved in transmission of HIV in the female genital tract.