TY - JOUR
T1 - Adherence of human immunodeficiency virus-infected lymphocytes to fetal placental cells
T2 - A model of maternal → fetal transmission
AU - Schwartz, David H.
AU - Sharma, Usha K.
AU - Perlman, Elizabeth J.
AU - Blakemore, Karin
PY - 1995/2/14
Y1 - 1995/2/14
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.92.4.978
DO - 10.1073/pnas.92.4.978
M3 - Article
C2 - 7862677
AN - SCOPUS:0028859227
SN - 0027-8424
VL - 92
SP - 978
EP - 982
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 4
ER -
