Maidji Ekaterina, Percivalle Elena, Gerna Giuseppe, Fisher Susan, Pereira Lenore
Department of Servizio di Virologia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, 27100, Pavia, Italy.
Virology. 2002 Dec 5;304(1):53-69. doi: 10.1006/viro.2002.1661.
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.
对感染人巨细胞病毒（CMV）的胎盘进行分析表明，病毒传播可能涉及绒毛中正在分化/具有侵袭性的细胞滋养层细胞，这些细胞将胎盘附着于子宫壁。为了剖析这一过程中的细胞成分，我们构建了一种共培养系统，使极化的子宫微血管内皮细胞（UtMVEC）感染一株内皮细胞嗜性的CMV致病株。然后我们评估了中性粒细胞和内皮细胞在感染传播至正在分化的细胞滋养层细胞过程中的潜在作用。免疫细胞化学和病毒复制分析结果显示，CMV优先通过顶端膜感染内皮细胞，并破坏细胞连接蛋白，从而改变细胞旁通透性和细胞极性。针对CMV糖蛋白B（一种促进病毒粒子穿透的包膜成分）的中和抗体可阻断极化UtMVEC中的噬斑形成。中性粒细胞将CMV感染传递给UtMVEC，后者继而感染细胞滋养层细胞。然而，中性粒细胞并不直接感染细胞滋养层细胞。这些发现表明，子宫微血管中的内皮细胞可能是锚定绒毛血管内细胞滋养层细胞CMV感染的潜在来源。可能妊娠子宫中的细胞因子/趋化因子环境会吸引免疫细胞，这些免疫细胞感染胎儿-母体混合血管中的内皮细胞。反过来，这些细胞可能感染血管内细胞滋养层细胞，这可能是导致胎盘CMV逆行感染的一系列事件的一个起始点。
