Douglas G C, Fry G N, Thirkill T, Holmes E, Hakim H, Jennings M, King B F
Department of Cell Biology, School of Medicine, University of California, Davis 95616.
AIDS Res Hum Retroviruses. 1991 Sep;7(9):735-40. doi: 10.1089/aid.1991.7.735.
In order to investigate how human immunodeficiency virus (HIV) gains entry to the placenta, we have performed in vitro experiments in which highly purified trophoblast cells isolated from term human placentas were examined for their susceptibility to HIV infection. Trophoblast cells were exposed to cell-free HIV-1 for up to 24 h, after which the cultures were monitored by p24 antigen capture assay, reverse transcriptase assay, and electron microscopy for evidence of virus uptake and replication. None was found. In the second series of experiments, trophoblast cells were cocultured with HIV-infected MOLT-4 cells for 24 h, stained using an anti-HIV antibody, and examined by immunofluorescence microscopy. The MOLT cells were strongly positive, as expected, but many trophoblast colonies also showed a punctate staining pattern. Examination of similar cultures using the electron microscope revealed MOLT cells adherent to trophoblast but no evidence of cell-cell fusion. Virions were observed in coated pits at the trophoblast cell surface and in endosomes or multivesicular bodies in the cytoplasm. These observations are consistent with an endocytosis-mediated mechanism of virus entry. Virions were also observed budding from the trophoblast plasma membrane, indicating that these cells can support HIV replication. To our knowledge, these results show for the first time that HIV can infect placental trophoblast cells in vitro. The results suggest that the placenta could become infected with HIV by the interaction of virus-infected maternal lymphocytes with syncytiotrophoblast bordering the maternal blood in the intervillous space.
为了研究人类免疫缺陷病毒（HIV）如何进入胎盘，我们进行了体外实验，检测从足月人胎盘中分离出的高度纯化的滋养层细胞对HIV感染的易感性。将滋养层细胞暴露于无细胞的HIV-1中长达24小时，之后通过p24抗原捕获试验、逆转录酶试验和电子显微镜监测培养物，以寻找病毒摄取和复制的证据。未发现相关证据。在第二系列实验中，将滋养层细胞与感染HIV的MOLT-4细胞共培养24小时，用抗HIV抗体染色，然后通过免疫荧光显微镜检查。正如预期的那样，MOLT细胞呈强阳性，但许多滋养层细胞集落也显示出点状染色模式。使用电子显微镜检查类似的培养物发现，MOLT细胞附着在滋养层细胞上，但没有细胞间融合的证据。在滋养层细胞表面的包被小窝以及细胞质中的内体或多囊泡体中观察到病毒颗粒。这些观察结果与内吞作用介导的病毒进入机制一致。还观察到病毒颗粒从滋养层细胞膜出芽，表明这些细胞可以支持HIV复制。据我们所知，这些结果首次表明HIV在体外可感染胎盘滋养层细胞。结果提示，在绒毛间隙中，病毒感染的母体淋巴细胞与邻接母体血液的合体滋养层细胞相互作用，可能导致胎盘感染HIV。
