Background: The virologic and cellular factors that are involved in transmission of HIV-1 across the female genital tissue are poorly understood. 

Methods: Using a human cervical tissue-derived organ culture model we investigated the role of phenotypic characteristics of HIV-1 and identified the cell types that are first infected during transmission. 

Results: Our data indicate that the cell-free R5 HIV-1 was more efficiently transmitted than cell-free X4 HIV-1.  Cell-free and cell-associated HIV-1 had comparable transmission efficiency regardless of whether the virus was of R5 or X4 type.  We have demonstrated that memory CD4+ T cells and not Langerhans cells were the first productively-infected cells localizing at the epithelial-submucosa junction 6 hours after virus exposure.  By 24 hours, the number of HIV-1 RNA-expressing memory CD4 cell increased and a small amount in macrophages was located on or immediately beneath the epithelial layer.  However, no dendritic cells were detected HIV-1 RNA positive by 24 hours.  Only 96 hours after exposure, productive infection of Langerhans dendritic cells along with memory CD4+ T cells and macrophages were detected.  Furthermore, PMPA, an antiretroviral compound and UC781, a microbicide inhibited HIV-1 transmission across the mucosa. 

Conclusions: This finding provides an alternative pathway for the dissemination of infection to the body in which early infection of T cells in genital mucosa would allow virus to expand rapidly and get transferred to the dendritic cells, which would then carry HIV-1 to draining lymph nodes.  The study also indicates the utility of the organ culture to screen topical microbicides for their ability to block sexual transmission of HIV-1.