SIV Replication and the Dendritic Cell

To evaluate the potential involvement of dendritic cells (DCs) in the mucosal transmission of HIV-1 we have used a model system of skin-derived DCs to study the cell-virus interactions in vitro. More recently we have extended these studies to the macaque system to further investigate DCs from a variety of more accessible tissues, particularly the mucosae. The DCs isolated from macaque body surfaces exhibit an almost identical phenotype and morphology to mature human DCs. Both CD4 ⁺ and CD8 ⁺ T cells are also present in the suspensions isolated from these tissues, with some T cells being tightly bound to the DCs. As in the human system, the skin-derived DCs support active replication of SIV in collaboration with syngeneic skin-derived T cells. Much of the virus is produced by multinucleated syncytia. On separation of the cell subsets by cell sorting, it was revealed that most active viral replication occurs in the DC-T cell conjugate fraction. Virus growth is also detected within the DC-T cell mixtures isolated from the nasopharyngeal and vaginal mucosae, but not in those isolated from the cervical mucosa. This animal model is being used to further dissect the role of DCs in the transmission and pathogenesis of infection with immunodeficiency viruses.