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

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

^*Corresponding author for this work

Clinical and Applied Virology

Research output: Contribution to journal › Article › Research › peer-review

2 Citations (Scopus)

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.

Original language	English
Article number	106352
Journal	iScience
Volume	26
Issue number	4
DOIs	https://doi.org/10.1016/j.isci.2023.106352
Publication status	Published - 21 Apr 2023

Keywords

Immunology
Virology

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title = "Rubella virus infection in endothelial cells reduces angiogenesis via interferon beta-induced CXCL10",

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",

author = "Vivien Henschke and Konstanze Hild and Erik Schilling and Jan Haas and Vanina Filipova and Stephan Erbe and Roman K{\"o}nig and H{\"u}bschen, {Judith M.} and Ulrich Laufs and Claudia Claus and Boeckel, {Jes Niels}",

note = "Funding Information: We thank Tino R{\"o}xe and Anne M{\"u}ller for excellent technical assistance. The authors want to thank Benedikt Weiβbrich, Institute for Virology and Immunobiology, University of Wuerzburg, Germany for provision of the RuV Wb12 strain. This work was funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) project number BO 5271/3-1 to JNB and through SFB 1052, project number 209933838, subproject C06 to JNB and UL. Publisher Copyright: {\textcopyright} 2023 The Authors",

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doi = "10.1016/j.isci.2023.106352",

language = "English",

volume = "26",

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TY - JOUR

T1 - Rubella virus infection in endothelial cells reduces angiogenesis via interferon beta-induced CXCL10

AU - Henschke, Vivien

AU - Hild, Konstanze

AU - Schilling, Erik

AU - Haas, Jan

AU - Filipova, Vanina

AU - Erbe, Stephan

AU - König, Roman

AU - Hübschen, Judith M.

AU - Laufs, Ulrich

AU - Claus, Claudia

AU - Boeckel, Jes Niels

N1 - Funding Information: We thank Tino Röxe and Anne Müller for excellent technical assistance. The authors want to thank Benedikt Weiβbrich, Institute for Virology and Immunobiology, University of Wuerzburg, Germany for provision of the RuV Wb12 strain. This work was funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) project number BO 5271/3-1 to JNB and through SFB 1052, project number 209933838, subproject C06 to JNB and UL. Publisher Copyright: © 2023 The Authors

PY - 2023/4/21

Y1 - 2023/4/21

N2 - 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.

AB - 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.

KW - Immunology

KW - Virology

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UR - https://pubmed.ncbi.nlm.nih.gov/37009214

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DO - 10.1016/j.isci.2023.106352

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VL - 26

JO - iScience

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M1 - 106352

ER -

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

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