Rubella virus infection in endothelial cells reduces angiogenesis via interferon betainduced CXCL10
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-ß 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-ß receptor. The data identify an important role for anti-viral IFN-mediated induction of CXCL10 in controlling EC function during RuV infection Overall design: Comparative gene expression analysis of RNA-seq data of endothelial cells after treatment with Rubella and/or IFN-ß and/or IFN-?1