Abstract
Worldwide most HIV infections occur through heterosexual transmission, involving complex interactions of cell-free and cell-associated particles with cells of the female genital tract mucosa. The ability of HIV-1 to “infect” epithelial cells remains poorly understood. To address this question, replicative-competent chimeric constructs expressing fluorescent proteins and harboring the envelope of X4- or R5-tropic HIV-1 strains were used to “infect” endometrial HEC1-A cells. The virus-cell interactions were visualized using confocal microscopy (CM) at various times post infection. Combined with quantification of viral RNA and total HIV DNA in infected cells, the CM pictures suggest that epithelial cells do not support a complete viral replication cycle: X4-tropic viruses are imported into the nucleus in a non-productive way, whereas R5-tropic viruses transit through the cytoplasm without replication and are preferentially transmitted to susceptible activated peripheral blood mononuclear cells. Within the limit of experiments conducted in vitro on a continued cell line, these results indicate that the epithelial mucosa may participate to the selection of HIV-1 strains at the mucosal level.
Highlights
Heterosexual transmission of HIV by semen from infected men to the genital mucosa of uninfected women is the main cause of new infections worldwide
The aim of the present study was to revise the debated issue of HIV-1 infection in genital epithelial cells by using confocal microscopy (CM) to visualize the fate of X4- or R5-tropic viruses in the HEC-1A cell line, a well-established in vitro model of endometrial epithelial cells [29,32]
One of the most important characteristics of epithelial cells is to be polarized with different apical and basal lipid and protein composition and to form selective barriers at the surface of the tissues [38]; the HEC-1A cell line was shown to exhibit this property when cultured on different supports including filters and solid surfaces like glass slides, as previously shown by transepithelial electrical measurements [12]
Summary
Heterosexual transmission of HIV by semen from infected men to the genital mucosa of uninfected women is the main cause of new infections worldwide. HIV is present in semen as cellassociated virus in non-spermatozoa mononuclear cells as well as cell-free particles. Diverse routes of transmission involving these two forms of viruses through the intact female genital mucosa have been described [1,2,3,4,5,6,7,8,9,10]. One model suggests that cell-free particles pass through the epithelial cells by transcytosis [1,11]. Seminal mononuclear cell-associated viruses may transmigrate through the female genital tract [12,13]. Dendritic cells and Langerhans cells were shown to play a key role in the transport of virions across the mucosa, as PLOS ONE | DOI:10.1371/journal.pone.0169453 January 6, 2017
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