Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosaafter intravaginal inoculation and infects intraepithelial dendritic cells

Despite recent insights into mucosal human immunodeficiency virus (HIV) tra nsmission, the route used by primate lentiviruses to traverse the stratifie d squamous epithelium of mucosal surfaces remains undefined. To determine i f dendritic cells (DC) are used by primate lentiviruses to traverse the epi thelial barrier of the genital tract, rhesus macaques were intravaginally e xposed to cell-free simian immunodeficiency virus SIVmac251. We examined fo rmalin-fixed tissues and HLA-DR+-enriched cell suspensions to identify the cells containing SN RNA in the genital tract and draining lymph nodes withi n the first 24 h of infection. Using SIV-specific fluorescent in situ hybri dization combined with immunofluorescent antibody labeling of lineage-speci fic cell markers, numerous SIV RNA(+) DC were documented in cell suspension s from the vaginal epithelium 18 h after vaginal inoculation. In addition, we determined the minimum time that the SIV inoculum must remain in contact with the genital mucosa for the virus to move from the vaginal lumen into the mucosa, We now show that SIV enters the vaginal mucosa within 60 min of intravaginal exposure, infecting primarily intraepithelial DC and that SIV -infected cells are located in draining lymph nodes within 18 h of intravag inal SIV exposure. The speed with which primate lentiviruses penetrate muco sal surfaces, infect DC, and disseminate to draining Lymph nodes poses a se rious challenge to HIV vaccine development.