Rubella virus infection in endothelial cells reduces angiogenesis via interferon beta-induced CXCL10

Vivien Henschke; Konstanze Hild; Erik Schilling; Jan Haas; Vanina Filipova; Stephan Erbe; Roman König; Judith M Hübschen; Ulrich Laufs; Claudia Claus; Jes-Niels Boeckel

doi:10.1016/j.isci.2023.106352

Rubella virus infection in endothelial cells reduces angiogenesis via interferon beta-induced CXCL10

iScience. 2023 Mar 7;26(4):106352. doi: 10.1016/j.isci.2023.106352. eCollection 2023 Apr 21.

Authors

Vivien Henschke¹, Konstanze Hild¹, Erik Schilling², Jan Haas^{3

4}, Vanina Filipova⁵, Stephan Erbe⁵, Roman König⁵, Judith M Hübschen⁶, Ulrich Laufs⁵, Claudia Claus¹, Jes-Niels Boeckel⁵

Affiliations

¹ Institute of Medical Microbiology and Virology, Medical Faculty, Leipzig University, Leipzig, Germany.
² Department of Internal Medicine III, Rheumatology Unit, Medical Faculty, Leipzig University, Leipzig, Germany.
³ Department of Internal Medicine III, University of Heidelberg, Heidelberg, Germany.
⁴ German Centre for Cardiovascular Research (DZHK), Partner site Heidelberg, Heidelberg, Germany.
⁵ Klinik und Poliklinik für Kardiologie, Universitätsklinikum Leipzig, 04103 Leipzig, Germany.
⁶ Department of Infection and Immunity, Luxembourg Institute of Health, 29 rue Henri Koch, 4354 Esch-sur-Alzette, Luxembourg.

Abstract

Rubella virus (RuV) infection during pregnancy can lead to abortion, stillbirth, and embryonic defects, resulting in congenital rubella syndrome (CRS). It is estimated that there are still 100,000 cases of CRS per year in developing regions with a mortality rate of over 30%. The molecular pathomechanisms remain largely unexplored. Placental endothelial cells (EC) are frequently infected with RuV. RuV reduced the angiogenic and migratory capacity of primary human EC, as confirmed by treatment of EC with serum from RuV IgM-positive patients. Next generation sequencing analysis revealed the induction of antiviral interferon (IFN) type I and III and CXCL10. The RuV-induced transcriptional profile resembled the effects of IFN-β treatment. The RuV-mediated inhibition of angiogenesis was reversed by treatment with blocking and neutralizing antibodies targeting CXCL10 and the IFN-β receptor. The data identify an important role for antiviral IFN-mediated induction of CXCL10 in the control of EC function during RuV infection.

Keywords: Immunology; Virology.