We have compared intravaginal infection efficiency between T-tropic SIVmac239 and its M-tropic chimera SIVmac239/17E in mature rhesus macaques, hypothesizing that macrophage tropic viruses would possess a distinct advantage for transmission across a mucosal surface. To date, 12 animals have been inoculated intravaginally with either SIVmac239 or SIVmac239/17E, and 2 additional macaques have been inoculated with immune-complexed virus. A significant difference in infection efficiency was not observed at high viral input (2 x 105 TCID50). These results suggest that in the SIV model, cell tropism does not affect the efficiency of infection across the reproductive mucosa of female macaques. Our current efforts are directed at investigating whether viral tropism influences efficiency of viral dissemination following mucosal infection, and comparing env sequences from viruses obtained from systemic versus mucosal lymphoid tissues during acute infection. Phenotype of i mmune cel ls at mucosal surfaces in macaques. Studies investigating the phenotype and distribution of immune cells that serve as potential targets of infection with SIV within the vaginal and cervical mucosa of rhesus macaques reveal that T cells and macrophages are diffusely distributed within the lamina propria at all levels of the alimentary mucosa, and occasionally occur within the mucosal epithelial cell layer. In addition to CD4+ T cells and macrophages, dendritic cells may serve as target cells of infection at mucosal sites, or may function to transport virus to subjacent organized lymphoid tissue. FUNDING NIH / NIAID $202,522 09/15/95 - 08/31/99 PUBLICATIONS Vincent, M.J., Martin, A.S. and Compans, R.W. Function of the KKXX motif in endoplasmic reticulum retention of a transmembrane protein depends on the length and structure of the cytoplasmic domain. J Biol Chem 273:950-956, 1998. P51RR00165-38 1/1/1998 - 12/31/1998 Yerkes Regional Primate Research Center