PDF(Pubmed)
Abstract：
The mechanism by which Zika virus (ZIKV) causes severe birth defects in pregnant women remains unclear. Cell tropisms in placenta and brain play a crucial role in ZIKV pathogenesis, leading to congenital Zika syndrome (CZS). To identify the host factors involved in ZIKV infection, we compared the transcriptional profiles of ZIKV-infected human first-trimester placental trophoblast cells HTR8/SVneo and a human glioblastoma astrocytoma cell line U251. Our results demonstrated that ZIKV exhibited lower rates of mRNA replication and protein expression in HTR8 than in U251 cells, while showing a higher release of infectious viral particles. However, a greater number of differentially expressed genes (DEGs) were found in ZIKV-infected U251 cells than in ZIKV-infected HTR8 cells. Several of these DEGs were enriched in distinct biological processes related to the characteristics of each cell type that may contribute to foetal damage. Both cell types exhibited activation of common interferons, inflammatory cytokines, and chemokine production upon ZIKV infection. Moreover, the neutralization of tumour necrosis factor-alpha (TNF-α) promoted ZIKV infection in both trophoblasts and glioblastoma astrocytoma cells. Overall, we identified multiple DEGs associated with ZIKV pathogenesis.
摘要：
寨卡病毒（ZIKV）导致孕妇严重出生缺陷的机制尚不清楚。胎盘和大脑中的细胞嗜性在ZIKV发病机制中起关键作用，导致先天性寨卡综合征（CZS）。为了确定参与ZIKV感染的宿主因素，我们比较了ZIKV感染的人早孕胎盘滋养层细胞HTR8/SVneo和人胶质母细胞瘤星形细胞瘤细胞系U251的转录谱。我们的结果表明，ZIKV在HTR8中的mRNA复制和蛋白表达率低于U251细胞。同时显示出更高的感染性病毒颗粒释放。然而,与ZIKV感染的HTR8细胞相比，在ZIKV感染的U251细胞中发现了更多的差异表达基因（DEGs）。这些DEG中的一些在与可能导致胎儿损伤的每种细胞类型的特征相关的不同生物过程中富集。两种细胞类型都表现出常见干扰素的激活，炎性细胞因子，和ZIKV感染时趋化因子的产生。此外，中和肿瘤坏死因子-α（TNF-α）可促进滋养细胞和胶质母细胞瘤星形细胞瘤细胞中的ZIKV感染。总的来说,我们确定了与ZIKV发病机制相关的多个DEGs。
