Cell-to-cell contact results in a selective translocation of maternal human immunodeficiency virus type 1 quasispecies across a trophoblastic barrierby both transcytosis and infection

Mother-to-child transmission can occur in utero, mainly intrapartum and pos tpartum in case of breastfeeding. In utero transmission is highly restricte d and results in selection of viral variant from the mother to the child. W e have developed an in vitro system that mimics the interaction between vir uses, infected cells present in maternal blood, and the trophoblast, the fi rst barrier protecting the fetus. Trophoblastic BeWo cells were grown as a tight polarized monolayer in a two-chamber system. Cell-free virions applie d to the apical pole neither crossed the barrier nor productively infected BeWo cells. In contrast, apical contact with human immunodeficiency virus ( HIV)-infected peripheral blood mononuclear cells (PBMCs) resulted in transc ytosis of infectious virus across the trophoblastic monolayer and in produc tive infection correlating with the fusion of HIV-infected PBMCs with troph oblasts. We showed that viral variants are selected during these two steps and that in one case of in utero transmission, the predominant maternal vir al variant characterized after transcytosis was phylogenetically indistingu ishable from the predominant child's virus. Hence, the first steps of trans mission of HIV-1 in utero appear to involve the interaction between HIV typ e 1-infected cells and the trophoblastic layer, resulting in the passage of infectious HIV by transcytosis and by fusion/infection, both leading to a selection of virus quasispecies.