? For successful heterosexual and vertical transmission, HIV first has to cross the mucosal barrier of the intestinal or genital tracts to infect CD4+ T cells. Although this initial transport of HIV through the epithelium is absolutely critical for HIV colonization, it has been poorly studied, and most importantly the mechanisms controlling this process remain obscure. To date, the initial step in the interaction between HIV and epithelial cells is the binding of HIV envelope glycoproteins to the epithelial cell galactosyl ceramide(GalCer) and the chemokine receptor CCR5. Although it has previously been postulated that GalCer substitutes for CD4 in HIV entry into epithelial cells, more recent studies suggest that fusion between viral and epithelial cell membrane does not occur. These observations strongly suggest that HIV utilizes unconventional mechanisms to enter primary epithelial cells. Importantly, we obtained several lines of evidence suggesting that heparan sulfate proteoglycans (HSPGs) play a critical role in HIV transcytosis through genital epithelial cell monolayers. Thus, we propose in the present study to fully identify the requirements for the apical-basal transport of HIV through the initial points of contacts with the virus, the genital and oral/intestinal epithelium. ? ? ?
