Infection of Macaques after Vaginal Exposure to Cell-Associated Simian Immunodeficiency Virus

Background. The contribution of infected semen cells to sexual transmission of human immunodeficiency virus (HIV) is still debated. We addressed this issue in the model of experimental infection of macaques with simian immunodeficiency virus (SIV). Methods. Frozen stocks of cells obtained from the spleen of macaques at the peak of SIVmac251 viremia were prepared. After being thawed and washed, cells were deposited at different concentrations in the vaginas of adult macaques treated with medroxyprogesterone acetate (Depo-Provera). To unravel mechanisms of infection, stock cells labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE) were inoculated intravaginally. Followup testing of samples from the mucosa and different lymphoid tissues obtained 21 and 45 h later was performed by flow cytometry, immunohistochemical analysis, and in situ hybridization. Results. Systemic and persistent infection was achieved after vaginal exposure of macaques to SIV-infected cells. The dose needed to infect 50% of females was 6.69 x 10(5) +/- 2.08 x 10(5) viral DNA copies. At days 1 and 2 after exposure to cell-associated SIV labeled with CFSE, SIV-positive cells were detected in proximal and distal lymphoid tissues. Conclusions. Infection with SIV after exposure of vaginal and cervical mucosa to cell-associated virus represents a new mechanism of sexual transmission of HIV and SIV that may have significant impacts in the development of preventive approaches like microbicides.