HIV-1 infection of Langerhans cells in a reconstructed vaginal mucosa.
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 azidothymidine, a reverse-transcriptase inhibitor, was also observed. Moreover, HIV-1-infected LCs of the reconstructed mucosa were able to transmit R5 or X4 HIV-1 strains to activated peripheral blood mononuclear cells. Such a model could be a useful tool to study the mechanisms involved in transmission of HIV in the female genital tract.
Sivard
Peggy
P
Groupe Immunite des Muqueuses et Agents Pathogenes, Jean Monnet University, Saint-Etienne, France.
Berlier
Willy
W
Picard
Bertrand
B
Sabido
Odile
O
Genin
Christian
C
Misery
Laurent
L
D019380:Anti-HIV Agents / Q000494:pharmacology; D018952:Antigens, CD34 / Q000032:analysis; D000998:Antiviral Agents / Q000494:pharmacology; D018946:Chemokine CCL5 / Q000494:pharmacology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D018920:Coculture Techniques; D046508:Culture Techniques; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development* / Q000302:isolation & purification; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007801:Langerhans Cells / Q000378:metabolism / Q000821:virology*; D007963:Leukocytes, Mononuclear / Q000821:virology; D009092:Mucous Membrane; D011533:Proviruses / Q000302:isolation & purification; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D015728:Receptors, HIV / Q000378:metabolism*; D014621:Vagina / Q000166:cytology* / Q000378:metabolism; D015215:Zidovudine / Q000494:pharmacology
D019380:Anti-HIV Agents; D018952:Antigens, CD34; D000998:Antiviral Agents; C515255:CXCL12 protein, human; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D004279:DNA, Viral; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D015728:Receptors, HIV; D015215:Zidovudine