{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T17:04:25Z","timestamp":1773248665128,"version":"3.50.1"},"reference-count":64,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R15AI35893"],"award-info":[{"award-number":["R15AI35893"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Health","award":["P20 GM103476"],"award-info":[{"award-number":["P20 GM103476"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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, Hexa, 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.<\/jats:p>","DOI":"10.3390\/cells10113085","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T12:46:23Z","timestamp":1636461983000},"page":"3085","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Murine Trophoblast Stem Cells and Their Differentiated Cells Attenuate Zika Virus In Vitro by Reducing Glycosylation of the Viral Envelope Protein"],"prefix":"10.3390","volume":"10","author":[{"given":"Biswas","family":"Neupane","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Biology, Center for Molecular and Cellular Biosciences, The University of Southern Mississippi, Hattiesburg, MS 39406, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona","family":"Fendereski","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Center for Molecular and Cellular Biosciences, The University of Southern Mississippi, Hattiesburg, MS 39406, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farzana","family":"Nazneen","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Center for Molecular and Cellular Biosciences, The University of Southern Mississippi, Hattiesburg, MS 39406, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-Lin","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Center for Molecular and Cellular Biosciences, The University of Southern Mississippi, Hattiesburg, MS 39406, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengwei","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Center for Molecular and Cellular Biosciences, The University of Southern Mississippi, Hattiesburg, MS 39406, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.chom.2016.03.010","article-title":"A Mouse Model of Zika Virus Pathogenesis","volume":"19","author":"Lazear","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Bai, F., Thompson, E.A., Vig, P.J.S., and Leis, A.A. 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