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Pluripotent Stem Cell-Based Models: A Peephole into Virus Infections during Early Pregnancy

1
Institute of Virology, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany
2
University Clinic and Outpatient Clinic for Psychiatry, Psychotherapy, Psychosomatic Medicine, Martin Luther University Halle-Wittenberg, 06112 Halle (Saale), Germany
3
Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, 4354 Esch-sur-Alzette, Luxembourg
*
Author to whom correspondence should be addressed.
Cells 2020, 9(3), 542; https://doi.org/10.3390/cells9030542
Received: 15 January 2020 / Revised: 14 February 2020 / Accepted: 21 February 2020 / Published: 26 February 2020
(This article belongs to the Special Issue Stem Cell-based Therapy and Disease Modeling)
The rubella virus (RV) was the first virus shown to be teratogenic in humans. The wealth of data on the clinical symptoms associated with congenital rubella syndrome is in stark contrast to an incomplete understanding of the forces leading to the teratogenic alterations in humans. This applies not only to RV, but also to congenital viral infections in general and includes (1) the mode of vertical transmission, even at early gestation, (2) the possible involvement of inflammation as a consequence of an activated innate immune response, and (3) the underlying molecular and cellular alterations. With the progress made in the development of pluripotent stem cell-based models including organoids and embryoids, it is now possible to assess congenital virus infections on a mechanistic level. Moreover, antiviral treatment options can be validated, and newly emerging viruses with a potential impact on human embryonal development, such as that recently reflected by the Zika virus (ZIKV), can be characterized. Here, we discuss human cytomegalovirus (HCMV) and ZIKV in comparison to RV as viruses with well-known congenital pathologies and highlight their analysis on current models for the early phase of human development. This includes the implications of their genetic variability and, as such, virus strain-specific properties for their use as archetype models for congenital virus infections. In this review, we will discuss the use of induced pluripotent stem cells (iPSC) and derived organoid systems for the study of congenital virus infections with a focus on their prominent aetiologies, HCMV, ZIKV, and RV. Their assessment on these models will provide valuable information on how human development is impaired by virus infections; it will also add new insights into the normal progression of human development through the analysis of developmental pathways in the context of virus-induced alterations. These are exciting perspectives for both developmental biology and congenital virology. View Full-Text
Keywords: teratogenesis; embryonal development; interferon; placenta; blastocyst; iPSC; pluripotent stem cells; organoid; cytomegalovirus; Zika virus; rubella virus; congenital virus infection teratogenesis; embryonal development; interferon; placenta; blastocyst; iPSC; pluripotent stem cells; organoid; cytomegalovirus; Zika virus; rubella virus; congenital virus infection
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Claus, C.; Jung, M.; Hübschen, J.M. Pluripotent Stem Cell-Based Models: A Peephole into Virus Infections during Early Pregnancy. Cells 2020, 9, 542.

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