Gene expression profiling of rubella virus infected primary endothelial cells of fetal and adult origin

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.

Alterations in Cell Mechanics by Actin Cytoskeletal Changes Correlate with Strain-Specific Rubella Virus Phenotypes for Cell Migration and Induction of Apoptosis

“…To confirm these findings, HUVECs as primary human endothelial cells were exemplarily infected with strains Therien and 07-00426. HUVEC are only slightly susceptible to RV-associated CPE development [ 34 ]. Thus, they were used to assess whether changes in cell mechanics are cell line-specific and dependent on CPE development.…”

Rubella Viruses Shift Cellular Bioenergetics to a More Oxidative and Glycolytic Phenotype with a Strain-Specific Requirement for Glutamine

“…However, in contrast to RV, this was connected with a high proton 2, and contraregulated transcripts in HUVECs and HSaVECs after RV infection that were assigned for biological process GO terms containing the word "mitochondria," "mitochondrion," "glutamine," or "glycolysis." Data were obtained from microarray analyses described elsewhere (24). (B) Identified hits and relevant target genes were confirmed by RT-qPCR for cDNA samples derived from the RNA extracted at 72 hpi from Wb-12-and 03-03703-infected Vero cells (MOI of 5).…”

“…Transcriptome analysis of Wb-12-infected HUVECs and human saphenous vein endothelial cells (HSaVECs) was carried out to identify possible metabolic targets addressed by RV. This analysis yielded 834 and 769 differentially expressed genes (DEGs), respectively (24). In order to detect Wb-12-induced alterations of metabolic pathways, the DEGs were analyzed for biological process GO terms containing the word "mitochondria," "mitochondrion," "glutamine," or "glycolysis."…”

Implications of TORCH Diseases in Retinal Development—Special Focus on Congenital Toxoplasmosis

“…The rubella virus non-structural protein, P90, can interact with important cell cycle regulators, retinoblastoma and cytokinesis-regulatory proteins, thus influencing cell cycle and apoptosis (Atreya et al, 2004; for a review, see George et al, 2019). Furthermore, downregulation of genes involved in sensory organs and eye development have also been reported by gene expression profiling of RV-infected human umbilical vein endothelial cells (HUVEC) (Geyer et al, 2016). RV infection can induce apoptosis in several cell types involving classic signaling pathways, leading to the activation of caspases, p53, p21, and Bcl-2 family proteins.…”