Adherence of human immunodeficiency virus-infected lymphocytes to fetal placental cells: a model of maternal --> fetal transmission.

Abstract

The precise timing and mechanism of in utero human immunodeficiency virus (HIV) infection are unknown, but transplacental transmission is likely. Term placentas from HIV+ pregnancies contain only rare HIV-infected cells whose origins and phenotypes remain controversial, and no correlation has been found between the presence of HIV in term placentas and transmission to offspring. Reports of trophoblast infectibility have not been reproducible and do not address the question of infection in the placental stroma, the cells in direct contact with fetal circulation. We report that primary cultures of fetal placental chorionic villus stromal cells, while not infectable in vitro, do support lethally irradiated HIV-infected peripheral blood mononuclear cells (PBMCs) in a form that permits rescue of HIV by activated PBMCs weeks later. Infected PBMCs adhere and become intimately associated with placental cells by a mechanism that is LFA-1 and CD4 independent but can be blocked by antibodies or soluble CD4 binding to cell surface-expressed HIV envelope. The ability to sustain infected irradiated cells was not shared by several trophoblast, fibroblast, or epithelial cell lines. This model has several features that are compatible with in utero transmission and allow testing of various agents proposed as interventions to block maternal-->fetal transmission. Placental stromal cells appear to inhibit apoptosis of HIV-infected, irradiated lymphocytes.