Murine Trophoblast Stem Cells and Their Differentiated Cells Attenuate Zika Virus In Vitro by Reducing Glycosylation of the Viral Envelope Protein

Zika virus (ZIKV) infection during pregnancy can cause devastating fetal neuropathological abnormalities, including microcephaly. Most studies of ZIKV infection in pregnancy have focused on post-implantation stage embryos. Currently, we have limited knowledge about how a pre-implantation stage embry...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Biswas Neupane, Mona Fendereski, Farzana Nazneen, Yan-Lin Guo, Fengwei Bai
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	trophoblast stem cells (TSCs) Zika virus envelop protein glycosylation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/f2687577492a4c9695d86bbf08713526
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f2687577492a4c9695d86bbf08713526
record_format	dspace
spelling	oai:doaj.org-article:f2687577492a4c9695d86bbf087135262021-11-25T17:11:22ZMurine Trophoblast Stem Cells and Their Differentiated Cells Attenuate Zika Virus In Vitro by Reducing Glycosylation of the Viral Envelope Protein10.3390/cells101130852073-4409https://doaj.org/article/f2687577492a4c9695d86bbf087135262021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3085https://doaj.org/toc/2073-4409Zika virus (ZIKV) infection during pregnancy can cause devastating fetal neuropathological abnormalities, including microcephaly. Most studies of ZIKV infection in pregnancy have focused on post-implantation stage embryos. Currently, we have limited knowledge about how a pre-implantation stage embryo deals with a viral infection. This study investigates ZIKV infection on mouse trophoblast stem cells (TSCs) and their in vitro differentiated TSCs (DTSCs), which resemble the cellular components of the trophectoderm layer of the blastocyst that later develops into the placenta. We demonstrate that TSCs and DTSCs are permissive to ZIKV infection; however, ZIKV propagated in TSCs and DTSCs exhibit substantially lower infectivity, as shown in vitro and in a mouse model compared to ZIKV that was generated in Vero cells or mouse embryonic fibroblasts (MEFs). We further show that the low infectivity of ZIKV propagated in TSCs and DTSCs is associated with a reduced level of glycosylation on the viral envelope (E) proteins, which are essential for ZIKV to establish initial attachment by binding to cell surface glycosaminoglycans (GAGs). The decreased level of glycosylation on ZIKV E is, at least, partially due to the low-level expression of a glycosylation-related gene, <i>Hexa</i>, in TSCs and DTSCs. Furthermore, this finding is not limited to ZIKV since similar observations have been made as to the chikungunya virus (CHIKV) and West Nile virus (WNV) propagated in TSCs and DTSCs. In conclusion, our results reveal a novel phenomenon suggesting that murine TSCs and their differentiated cells may have adapted a cellular glycosylation system that can limit viral infectivity by altering the glycosylation of viral envelope proteins, therefore serving as a unique, innate anti-viral mechanism in the pre-implantation stage embryo.Biswas NeupaneMona FendereskiFarzana NazneenYan-Lin GuoFengwei BaiMDPI AGarticletrophoblast stem cells (TSCs)Zika virusenvelop proteinglycosylationBiology (General)QH301-705.5ENCells, Vol 10, Iss 3085, p 3085 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	trophoblast stem cells (TSCs) Zika virus envelop protein glycosylation Biology (General) QH301-705.5
spellingShingle	trophoblast stem cells (TSCs) Zika virus envelop protein glycosylation Biology (General) QH301-705.5 Biswas Neupane Mona Fendereski Farzana Nazneen Yan-Lin Guo Fengwei Bai Murine Trophoblast Stem Cells and Their Differentiated Cells Attenuate Zika Virus In Vitro by Reducing Glycosylation of the Viral Envelope Protein
description	Zika virus (ZIKV) infection during pregnancy can cause devastating fetal neuropathological abnormalities, including microcephaly. Most studies of ZIKV infection in pregnancy have focused on post-implantation stage embryos. Currently, we have limited knowledge about how a pre-implantation stage embryo deals with a viral infection. This study investigates ZIKV infection on mouse trophoblast stem cells (TSCs) and their in vitro differentiated TSCs (DTSCs), which resemble the cellular components of the trophectoderm layer of the blastocyst that later develops into the placenta. We demonstrate that TSCs and DTSCs are permissive to ZIKV infection; however, ZIKV propagated in TSCs and DTSCs exhibit substantially lower infectivity, as shown in vitro and in a mouse model compared to ZIKV that was generated in Vero cells or mouse embryonic fibroblasts (MEFs). We further show that the low infectivity of ZIKV propagated in TSCs and DTSCs is associated with a reduced level of glycosylation on the viral envelope (E) proteins, which are essential for ZIKV to establish initial attachment by binding to cell surface glycosaminoglycans (GAGs). The decreased level of glycosylation on ZIKV E is, at least, partially due to the low-level expression of a glycosylation-related gene, <i>Hexa</i>, in TSCs and DTSCs. Furthermore, this finding is not limited to ZIKV since similar observations have been made as to the chikungunya virus (CHIKV) and West Nile virus (WNV) propagated in TSCs and DTSCs. In conclusion, our results reveal a novel phenomenon suggesting that murine TSCs and their differentiated cells may have adapted a cellular glycosylation system that can limit viral infectivity by altering the glycosylation of viral envelope proteins, therefore serving as a unique, innate anti-viral mechanism in the pre-implantation stage embryo.
format	article
author	Biswas Neupane Mona Fendereski Farzana Nazneen Yan-Lin Guo Fengwei Bai
author_facet	Biswas Neupane Mona Fendereski Farzana Nazneen Yan-Lin Guo Fengwei Bai
author_sort	Biswas Neupane
title	Murine Trophoblast Stem Cells and Their Differentiated Cells Attenuate Zika Virus In Vitro by Reducing Glycosylation of the Viral Envelope Protein
title_short	Murine Trophoblast Stem Cells and Their Differentiated Cells Attenuate Zika Virus In Vitro by Reducing Glycosylation of the Viral Envelope Protein
title_full	Murine Trophoblast Stem Cells and Their Differentiated Cells Attenuate Zika Virus In Vitro by Reducing Glycosylation of the Viral Envelope Protein
title_fullStr	Murine Trophoblast Stem Cells and Their Differentiated Cells Attenuate Zika Virus In Vitro by Reducing Glycosylation of the Viral Envelope Protein
title_full_unstemmed	Murine Trophoblast Stem Cells and Their Differentiated Cells Attenuate Zika Virus In Vitro by Reducing Glycosylation of the Viral Envelope Protein
title_sort	murine trophoblast stem cells and their differentiated cells attenuate zika virus in vitro by reducing glycosylation of the viral envelope protein
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f2687577492a4c9695d86bbf08713526
work_keys_str_mv	AT biswasneupane murinetrophoblaststemcellsandtheirdifferentiatedcellsattenuatezikavirusinvitrobyreducingglycosylationoftheviralenvelopeprotein AT monafendereski murinetrophoblaststemcellsandtheirdifferentiatedcellsattenuatezikavirusinvitrobyreducingglycosylationoftheviralenvelopeprotein AT farzananazneen murinetrophoblaststemcellsandtheirdifferentiatedcellsattenuatezikavirusinvitrobyreducingglycosylationoftheviralenvelopeprotein AT yanlinguo murinetrophoblaststemcellsandtheirdifferentiatedcellsattenuatezikavirusinvitrobyreducingglycosylationoftheviralenvelopeprotein AT fengweibai murinetrophoblaststemcellsandtheirdifferentiatedcellsattenuatezikavirusinvitrobyreducingglycosylationoftheviralenvelopeprotein
_version_	1718412687858204672

Murine Trophoblast Stem Cells and Their Differentiated Cells Attenuate Zika Virus In Vitro by Reducing Glycosylation of the Viral Envelope Protein

Ejemplares similares