Project description:Rubella virus infection during pregnancy can result in abortion, stillbirth and severe defects in embryogenesis resulting in congenital rubella syndrome (CRS). Low vaccination coverage in developing regions results in estimated 100,000 CRS cases in infants per year with a mortality rate over 30%. The molecular pathomechanisms and potential treatments remain largely unexplored. Endothelial cells (EC) of the placenta are infected by rubella virus (RuV). RuV reduced angiogenic and migratory capacity of primary human EC whereas cell cycle and apoptosis rate were not affected. Next generation sequencing analysis revealed an induction of antiviral type I and III interferons (IFN) that induced angiogenesis-inhibiting cytokines such as CXCL10. The transcriptional profile induced by RuV resembled the effects of IFN-β treatment. The cell culture data were confirmed using human serum from RuV IgM-positive patients that showed similar increase in CXCL10 and inhibited angiogenesis. RuV-mediated inhibition of angiogenesis was reversed by treatment with blocking and neutralizing antibodies targeting CXCL10 and IFN-β receptor. The data identify an important role for anti-viral IFN-mediated induction of CXCL10 in controlling EC function during RuV infection
Project description:We describe the transcriptional response to infection of human umbilical vein endothelial cells (Huvec) with different rubella virus strains
Project description:This study uses proteome microarray technology/data to identify predictive biomarkers of neutralizing antibody response and potential new correlates of protective immunity in rubella virus serology.
Project description:RNA was extracted from whole blood of subjects collected in Tempus tubes on day 0 (immediately prior to vaccination), day 1 and 3 post-vaccination. We performed gene expression analysis of subjects with similar baseline antibody titres to rubella virus (RV) that experienced an increase in anti-RV IgG titre (>= 2-fold) or not (< 2 fold) at one month post-vaccination.
