Transmission of human cytomegalovirus from infected uterine microvascular endothelial cells to differentiating/invasive placental cytotrophoblasts
Transmission of human cytomegalovirus from infected uterine microvascular endothelial cells to differentiating/invasive placental cytotrophoblasts
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DOI：
10.1006/viro.2002.1661
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发表时间：
2002-12-05
期刊：
影响因子：
3.7
通讯作者：
Pereira, L
中科院分区：
文献类型：
--
作者：
Maidji, E;Percivalle, E;Pereira, L
对感染人巨细胞病毒（CMV）的胎盘的分析表明，病毒传播可能涉及将胎盘附着在子宫壁上的绒毛中分化/侵入的细胞滋养层。为了解析这个过程中的细胞成分，我们开发了一种极化子宫微血管内皮细胞（UtMVEC）感染与CMV内皮细胞亲性致病株的共培养系统。然后我们评估了中性粒细胞和内皮细胞在感染扩散到分化的细胞滋养层中的潜在作用。免疫细胞化学和病毒复制分析表明，巨细胞病毒优先通过顶膜感染内皮细胞并破坏细胞连接蛋白，从而改变细胞旁通透性和细胞极性。 CMV 糖蛋白 B（一种促进病毒粒子渗透的包膜成分）的中和抗体可阻止极化 UtMVEC 中斑块的形成。中性粒细胞将 CMV 感染传播给 UtMVEC，UtMVEC 又感染细胞滋养层。然而，中性粒细胞并不直接感染细胞滋养层。这些发现表明子宫微脉管系统的内皮细胞是锚定绒毛血管内细胞滋养层 CMV 感染的潜在来源。怀孕子宫中的细胞因子/趋化因子环境可能会吸引免疫细胞，从而感染胎儿-母体混合血管中的内皮细胞。反过来，这些细胞可以感染血管内细胞滋养层，这是导致逆行性胎盘巨细胞病毒感染的级联反应的一个可能的起始点。 (C) 2002 年爱思唯尔科学（美国）。
Analysis of placentas infected with human cytomegalovirus (CMV) suggested that viral transmission could involve differentiating/invasive cytotrophoblasts in villi that attach the placenta to the uterine wall. To parse the cellular components in this process, we developed a coculture system of polarized uterine microvascular endothelial cell (UtMVEC) infection with an endothelial cell-tropic pathogenic strain of CMV Then we evaluated the potential role of neutrophils and endothelial cells in the spread of infection to differentiating cytotrophoblasts. As shown by immunocytochemistry and analysis of viral replication, CMV preferentially infected endothelial cells via apical membranes and disrupted cell junction proteins, thereby altering paracellular permeability and cell polarity. Neutralizing antibodies to CMV glycoprotein B, an envelope component that facilitates virion penetration, blocked plaque formation in polarized UtMVEC. Neutrophils transmitted CMV infection to UtMVEC, which in turn infected cytotrophoblasts. However, neutrophils did not directly infect cytotrophoblasts. These findings implicate endothelial cells from the uterine microvasculature as a potential source for CMV infection of endovascular cytotrophoblasts of the anchoring villi. Possibly the cytokine/chemokine milieu in the pregnant uterus could attract immune cells that infect endothelial cells in hybrid fetal-maternal vessels. In turn, these cells could infect endovascular cytotrophoblasts, one possible initiation point of a cascade that results in retrograde placental CMV infection. (C) 2002 Elsevier Science (USA).