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Open AccessArticle

Coxsackievirus B3 Infection of Human iPSC Lines and Derived Primary Germ-Layer Cells Regarding Receptor Expression

1
Institute of Medical Microbiology and Virology, Medical Faculty, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany
2
Institute of Biochemistry, Berlin Institute of Health (BIH) and Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 10117 Berlin, Germany
3
DZHK (German Centre for Cardiovascular Research), Partner Side, 10115 Berlin, Germany
4
Interdisciplinary Center for Bioinformatics, University of Leipzig, 04107 Leipzig, Germany
5
Department of Psychiatry, Psychotherapy, and Psychosomatic Medicine, Martin Luther University Halle Wittenberg, Julius-Kuehn-Strasse 7, 06112 Halle (Saale), Germany
6
Institute for Medical Physics and Biophysics, Medical Faculty, University of Leipzig, Härtelstrasse 16-18, 04107 Leipzig, Germany
*
Author to whom correspondence should be addressed.
Current address: Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University, Medical School, Pauwelstrasse 30, 52074 Aachen, Germany.
Academic Editor: Rivka Ofir
Int. J. Mol. Sci. 2021, 22(3), 1220; https://doi.org/10.3390/ijms22031220
Received: 13 December 2020 / Revised: 13 January 2021 / Accepted: 14 January 2021 / Published: 27 January 2021
(This article belongs to the Special Issue hiPSC-Derived Cells as Models for Drug Discovery)
The association of members of the enterovirus family with pregnancy complications up to miscarriages is under discussion. Here, infection of two different human induced pluripotent stem cell (iPSC) lines and iPSC-derived primary germ-layer cells with coxsackievirus B3 (CVB3) was characterized as an in vitro cell culture model for very early human development. Transcriptomic analysis of iPSC lines infected with recombinant CVB3 expressing enhanced green fluorescent protein (EGFP) revealed a reduction in the expression of pluripotency genes besides an enhancement of genes involved in RNA metabolism. The initial distribution of CVB3-EGFP-positive cells within iPSC colonies correlated with the distribution of its receptor coxsackie- and adenovirus receptor (CAR). Application of anti-CAR blocking antibodies supported the requirement of CAR, but not of the co-receptor decay-accelerating factor (DAF) for infection of iPSC lines. Among iPSC-derived germ-layer cells, mesodermal cells were especially vulnerable to CVB3-EGFP infection. Our data implicate further consideration of members of the enterovirus family in the screening program of human pregnancies. Furthermore, iPSCs with their differentiation capacity into cell populations of relevant viral target organs could offer a reliable screening approach for therapeutic intervention and for assessment of organ-specific enterovirus virulence. View Full-Text
Keywords: ectoderm; mesoderm; endoderm; human development; embryogenesis; CAR; CXADR; DAF; self-organizing maps; genome portrayal ectoderm; mesoderm; endoderm; human development; embryogenesis; CAR; CXADR; DAF; self-organizing maps; genome portrayal
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MDPI and ACS Style

Böhnke, J.; Pinkert, S.; Schmidt, M.; Binder, H.; Bilz, N.C.; Jung, M.; Reibetanz, U.; Beling, A.; Rujescu, D.; Claus, C. Coxsackievirus B3 Infection of Human iPSC Lines and Derived Primary Germ-Layer Cells Regarding Receptor Expression. Int. J. Mol. Sci. 2021, 22, 1220. https://doi.org/10.3390/ijms22031220

AMA Style

Böhnke J, Pinkert S, Schmidt M, Binder H, Bilz NC, Jung M, Reibetanz U, Beling A, Rujescu D, Claus C. Coxsackievirus B3 Infection of Human iPSC Lines and Derived Primary Germ-Layer Cells Regarding Receptor Expression. International Journal of Molecular Sciences. 2021; 22(3):1220. https://doi.org/10.3390/ijms22031220

Chicago/Turabian Style

Böhnke, Janik; Pinkert, Sandra; Schmidt, Maria; Binder, Hans; Bilz, Nicole C.; Jung, Matthias; Reibetanz, Uta; Beling, Antje; Rujescu, Dan; Claus, Claudia. 2021. "Coxsackievirus B3 Infection of Human iPSC Lines and Derived Primary Germ-Layer Cells Regarding Receptor Expression" Int. J. Mol. Sci. 22, no. 3: 1220. https://doi.org/10.3390/ijms22031220

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