ADHERENCE OF HUMAN IMMUNODEFICIENCY VIRUS-INFECTED LYMPHOCYTES TO FETAL-PLACENTAL CELLS - A MODEL OF MATERNAL-]FETAL TRANSMISSION

The precise timing and mechanism of in utero human immunodeficiency vi rus (HIV) infection are unknown, but transplacental transmission is li kely. Term placentas from HIV+ pregnancies contain only rare HIV-infec ted cells whose origins and phenotypes remain controversial, and no co rrelation has been found between the presence of HIV in term placentas and transmission to offspring. Reports of trophoblast infectibility h ave not been reproducible and do not address the question of infection in the placental stroma, the cells in direct contact with fetal circu lation. We report that primary cultures of fetal placental chorionic v illus stromal cells, while not infectable in vitro, do support lethall y irradiated HIV-infected peripheral blood mononuclear cells (PBMCs) i n a form that permits rescue of HIV by activated PBMCs weeks later, In fected PBMCs adhere and become intimately associated with placental ce lls by a mechanism that is LFA-1 and CD4 independent but can be blocke d by antibodies or soluble CD4 binding to cell surface-expressed HIV e nvelope. The ability to sustain infected irradiated cells was not shar ed by several trophoblast, fibroblast, or epithelial cell lines. This model has several features that are compatible with in utero transmiss ion and allow testing of various agents proposed as interventions to b lock maternal --> fetal transmission. Placental stromal cells appear t o inhibit apoptosis of HIV-infected, irradiated lymphocytes.