Simian Immunodeficiency Virus Rapidly Penetrates the Cervicovaginal Mucosa after Intravaginal Inoculation and Infects Intraepithelial Dendritic Cells

TLDR

The route by which primate lentiviruses cross the stratified squamous epithelium of mucosal surfaces remains undefined despite recent insights into mucosal HIV transmission. The study aimed to determine whether dendritic cells mediate traversal of the genital tract epithelium by primate lentiviruses by intravaginally exposing rhesus macaques to cell‑free SIVmac251. Researchers examined formalin‑fixed tissues and HLA‑DR+ enriched cell suspensions, using fluorescent in situ hybridization and immunofluorescence to identify SIV RNA‑positive dendritic cells in the vaginal epithelium and draining lymph nodes within 24 h, and measured the minimal contact time required for viral penetration. SIV entered the vaginal mucosa within 60 min, infected primarily intraepithelial dendritic cells, and reached draining lymph nodes within 18 h, highlighting the rapid penetration that challenges HIV vaccine development.

Abstract

ABSTRACT Despite recent insights into mucosal human immunodeficiency virus (HIV) transmission, the route used by primate lentiviruses to traverse the stratified squamous epithelium of mucosal surfaces remains undefined. To determine if dendritic cells (DC) are used by primate lentiviruses to traverse the epithelial barrier of the genital tract, rhesus macaques were intravaginally exposed to cell-free simian immunodeficiency virus SIVmac251. We examined formalin-fixed tissues and HLA-DR + -enriched cell suspensions to identify the cells containing SIV RNA in the genital tract and draining lymph nodes within the first 24 h of infection. Using SIV-specific fluorescent in situ hybridization combined with immunofluorescent antibody labeling of lineage-specific cell markers, numerous SIV RNA + DC were documented in cell suspensions 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 intravaginal SIV exposure. The speed with which primate lentiviruses penetrate mucosal surfaces, infect DC, and disseminate to draining lymph nodes poses a serious challenge to HIV vaccine development.