Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
J Virol. 2013 Aug;87(15):8569-81. doi: 10.1128/JVI.00708-13. Epub 2013 May 29.
Maternal-fetal transmission of group B coxsackieviruses (CVB) during pregnancy has been associated with a number of diverse pathological outcomes, including hydrops fetalis, fetal myocarditis, meningoencephalitis, neurodevelopmental delays, congenital skin lesions, miscarriage, and/or stillbirth. Throughout pregnancy, the placenta forms a critical antimicrobial protective barrier at the maternal-fetal interface. Despite the severity of diseases accompanying fetal CVB infections, little is known regarding the strategies used by CVB to gain entry into placental trophoblasts. Here we used both a trophoblast cell line and primary human trophoblasts to demonstrate the mechanism by which CVB gains entry into polarized placental trophoblasts. Our studies revealed that the kinetics of CVB entry into placental trophoblasts are similar to those previously described for polarized intestinal epithelial cells. Likewise, CVB entry into placental trophoblasts requires decay-accelerating factor (DAF) binding and involves relocalization of the virus from the apical surface to intercellular tight junctions. In contrast, we have identified a divergent mechanism for CVB entry into polarized trophoblasts that is clathrin, caveolin-1, and dynamin II independent but requires intact lipid rafts. In addition, we found that members of the Src family of tyrosine kinases were required for CVB entry. Our studies highlight the complexity of viral entry into human placental trophoblasts and may serve as a model for mechanisms used by diverse pathogens to penetrate the placental barrier.
在怀孕期间，B 组柯萨奇病毒（CVB）经母体向胎儿传播与多种不同的病理结果有关，包括胎儿水肿、胎儿心肌炎、脑膜脑炎、神经发育迟缓、先天性皮肤损伤、流产和/或死产。在整个怀孕期间，胎盘在母体-胎儿界面形成一个关键的抗微生物保护屏障。尽管伴随胎儿 CVB 感染的疾病很严重，但对于 CVB 进入胎盘滋养层的策略知之甚少。在这里，我们使用滋养层细胞系和原代人滋养层来证明 CVB 进入极化胎盘滋养层的机制。我们的研究表明，CVB 进入胎盘滋养层的动力学与先前描述的极化肠上皮细胞相似。同样，CVB 进入胎盘滋养层需要衰变加速因子（DAF）结合，并涉及病毒从顶端表面到细胞间紧密连接的重新定位。相比之下，我们已经确定了 CVB 进入极化滋养层的不同机制，该机制与网格蛋白、 caveolin-1 和 dynamin II 无关，但需要完整的脂筏。此外，我们发现Src 家族酪氨酸激酶成员是 CVB 进入所必需的。我们的研究强调了病毒进入人胎盘滋养层的复杂性，并可能成为多种病原体穿透胎盘屏障所使用的机制的模型。
