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Zika Virus Nonstructural Protein 1 Disrupts Glycosaminoglycans and Causes Permeability in Developing Human Placentas.
The Journal of Infectious Diseases ( IF 6.4 ) Pub Date : 2019-06-27 , DOI: 10.1093/infdis/jiz331
Henry Puerta-Guardo 1 , Takako Tabata 2 , Matthew Petitt 2 , Milena Dimitrova 1 , Dustin R Glasner 1 , Lenore Pereira 2 , Eva Harris 1
Affiliation  

BACKGROUND During pregnancy, the Zika flavivirus (ZIKV) infects human placentas, inducing defects in the developing fetus. The flavivirus nonstructural protein 1 (NS1) alters glycosaminoglycans on the endothelium, causing hyperpermeability in vitro and vascular leakage in vivo in a tissue-dependent manner. The contribution of ZIKV NS1 to placental dysfunction during ZIKV infection remains unknown. METHODS We examined the effect of ZIKV NS1 on expression and release of heparan sulfate (HS), hyaluronic acid (HA), and sialic acid on human trophoblast cell lines and anchoring villous explants from first-trimester placentas infected with ZIKV ex vivo. We measured changes in permeability in trophoblasts and stromal cores using a dextran-based fluorescence assay and changes in HA receptor expression using immunofluorescent microscopy. RESULTS ZIKV NS1 in the presence and absence of ZIKV increased the permeability of anchoring villous explants. ZIKV NS1 induced shedding of HA and HS and altered expression of CD44 and lymphatic endothelial cell HA receptor-1, HA receptors on stromal fibroblasts and Hofbauer macrophages in villous cores. Hyaluronidase was also stimulated in NS1-treated trophoblasts. CONCLUSIONS These findings suggest that ZIKV NS1 contributes to placental dysfunction via modulation of glycosaminoglycans on trophoblasts and chorionic villi, resulting in increased permeability of human placentas.

中文翻译:

寨卡病毒非结构蛋白1破坏糖胺聚糖并导致人类胎盘发育中的通透性。

背景技术在怀孕期间,寨卡黄病毒(ZIKV)感染人胎盘,导致发育中的胎儿出现缺陷。黄病毒非结构蛋白1(NS1)改变内皮上的糖胺聚糖,以组织依赖性方式导致体外通透性过高和体内血管渗漏。在ZIKV感染期间ZIKV NS1对胎盘功能障碍的贡献仍然未知。方法我们研究了ZIKV NS1对人滋养层细胞系和锚定来自体外感染ZIKV的早孕胎盘的绒毛外植体的硫酸乙酰肝素(HS),透明质酸(HA)和唾液酸的表达和释放的影响。我们使用基于葡聚糖的荧光测定法测量了滋养细胞和基质核心的通透性变化,并使用免疫荧光显微镜观察了HA受体表达的变化。结果ZIKV NS1在存在和不存在ZIKV的情况下都增加了锚定绒毛外植体的通透性。ZIKV NS1诱导HA和HS脱落,并改变绒毛核心中成纤维细胞和Hofbauer巨噬细胞上CD44和淋巴管内皮细胞HA受体1,HA受体的表达。在NS1处理的滋养细胞中也刺激了透明质酸酶。结论这些发现表明ZIKV NS1通过调节滋养细胞和绒毛膜绒毛上的糖胺聚糖导致胎盘功能障碍,从而导致人胎盘的通透性增加。绒毛状核中基质成纤维细胞和Hofbauer巨噬细胞上的HA受体。在NS1处理的滋养细胞中也刺激了透明质酸酶。结论这些发现表明ZIKV NS1通过调节滋养细胞和绒毛膜绒毛上的糖胺聚糖导致胎盘功能障碍,从而导致人胎盘的通透性增加。绒毛状核中基质成纤维细胞和Hofbauer巨噬细胞上的HA受体。在NS1处理的滋养细胞中也刺激了透明质酸酶。结论这些发现表明ZIKV NS1通过调节滋养细胞和绒毛膜绒毛上的糖胺聚糖导致胎盘功能障碍,从而导致人胎盘的通透性增加。
更新日期:2019-12-30
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