Gene expression profiling of rubella virus infected primary endothelial cells of fetal and adult origin
Gene expression profiling of rubella virus infected primary endothelial cells of fetal and adult origin
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DOI：
10.1186/s12985-016-0475-9
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发表时间：
2016-02-02
期刊：
影响因子：
4.8
通讯作者：
Mankertz, Annette
中科院分区：
文献类型：
--
作者：
Geyer, Henriette;Bauer, Michael;Mankertz, Annette
背景：风疹病毒（RV）感染通常是儿童和成人的轻度疾病。然而，母亲在怀孕的头三个月感染可导致婴儿先天性风疹综合征（CRS）。CRS胎仔显示心脏和血管内皮受损;因此，推测CRS相关临床表现可能是RV持续感染内皮细胞的结果。在这里，我们比较了RV感染对胎儿（HUVEC）和成人（HSaVEC）起源的原代内皮细胞（HSaVEC）基因表达的影响，通过转录profiling.Results：超过75%的基因差异调节以下RV感染是相同的两种细胞类型。基因本体论（GO）分析这些共同调控的基因显示了丰富的术语参与细胞因子的产生和细胞因子的调节。RV感染后炎性细胞因子的积累增加被蛋白质微阵列证实。有趣的是，趋化因子CCL 14，这是在胎儿-母体界面支持胚胎植入的牵连，下调RV感染后，只有在HUVEC。最值得注意的是，当分析每种细胞类型的独特调节的转录物时，HUVEC的下调基因的基于GO术语的聚类分析揭示了GO术语“感觉器官发育”、“耳发育”和“眼发育”的富集。由于视觉和听力受损是CRS患者中观察到的最突出的临床表现，在此检测到的参与感觉器官发育的下调基因揭示了可能有助于RV致畸作用的分子机制。
Background: Rubella virus (RV) infection is usually a mild illness in children and adults. However, maternal infection during the first trimester of pregnancy can lead to congenital rubella syndrome (CRS) in the infant. Fetuses with CRS show damage to the endothelium of the heart and blood vessels; thus, it has been speculated that the clinical manifestations associated with CRS may be a result of endothelial cells persistently infected with RV. Here, we compared the effects of RV infection on gene expression in primary endothelial cells of fetal (HUVEC) and of adult (HSaVEC) origin by transcriptional profiling.Results: More than 75 % of the genes differentially regulated following RV infection were identical in both cell types. Gene Ontology (GO) analysis of these commonly regulated genes showed an enrichment of terms involved in cytokine production and cytokine regulation. Increased accumulation of inflammatory cytokines following RV infection was verified by protein microarray. Interestingly, the chemokine CCL14, which is implicated in supporting embryo implantation at the fetal-maternal interface, was down-regulated following RV infection only in HUVEC. Most noticeably, when analyzing the uniquely regulated transcripts for each cell type, GO term-based cluster analysis of the down-regulated genes of HUVEC revealed an enrichment of the GO terms "sensory organ development", "ear development" and "eye development".Conclusion: Since impairment in vision and hearing are the most prominent clinical manifestations observed in CRS patients, the here detected down-regulated genes involved in the development of sensory organs sheds light on the molecular mechanisms that may contribute to the teratogenic effect of RV.