CELLULAR PATHWAY OF VAGINAL SIV INFECTION

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Significance HIV is a sexually transmitted disease and a vaccine capable of preventing sexual transmission of HIV should elicit mucosal immune responses in the genital tract. Objectives The major goal of this project is to define the early target cells and route of virus dissemination following intravaginal SIV inoculation. Results To determine the range of target cells in the genital that can be infected with SIV, detailed analysis of infected cells was undertaken in chronically-infected animals. In addition to T cells, we found numerous SIV-infected dendritic cells in the genital tract. This is the first in-vivo description of lentivirus-infected dendritic cells. To determine the earliest cells types infected after inoculation, 2 animals were killed at 24 hours and 2 animals were killed at 18 hours post-inoculation. SIV-infected cells were found at 18 hours in the genital tract. Work to characterize these cells is underway. Future Directions Use GFP-expressing SIV vectors to document the initial cell type infected after vaginal or oral inoculation. KEY WORDS vaccine protection, mucosal immunity, SIV vaginal transmission FUNDING NIH Grants AI39435 and RR00169 PUBLICATIONS Hu J., M. Pope, C. Brown, U. O'Doherty, C.J. Miller. Immunophenotypic characterization of SIV-infected dendritic cells in cervix, vagina and draining lymph nodes of rhesus monkeys. Lab. Invest. 78:435-451, 1998. Miller C.J. Localization of simian immunodeficiency virus infected cells in the genital tract of male and female rhesus macaques. J. Reprod. Immunol. 41:331-339, 1999.