Abstract
BackgroundRubella 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.ResultsMore 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”.ConclusionSince 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-016-0475-9) contains supplementary material, which is available to authorized users.
Highlights
IntroductionMaternal infection during the first trimester of pregnancy can lead to congenital rubella syndrome (CRS) in the infant
Rubella virus (RV) infection is usually a mild illness in children and adults
Since endothelial cells are believed to play a major role in RV-induced teratogenesis, our studies focused on the gene expression changes of an infection caused by a wild type RV isolate (Wuerzburg-12) in primary fetal endothelial cells derived from the human umbilical vein (HUVEC) and adult endothelial cells derived from the human saphenous vein (HSaVEC)
Summary
Maternal infection during the first trimester of pregnancy can lead to congenital rubella syndrome (CRS) in the infant. Maternal infection early in pregnancy can lead to a combination of birth defects in infants, collectively called congenital rubella syndrome (CRS) [1, 2]. Most of these findings are derived from studies using immortalized adult cell lines (e.g. Vero, A549, and BHK-21 cells). These cell lines differ considerably from fetal cells in vivo in terms of gene expression, metabolism, and growth rate, and give only limited insight into the effects of RV infection during embryonic development
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