Isogenic human trophectoderm cells demonstrate the role of NDUFA4 and associated variants in ZIKV infection Journal Article
| Authors: | Yang, L.; Han, Y.; Zhou, T.; Lacko, L. A.; Saeed, M.; Tan, C.; Danziger, R.; Zhu, J.; Zhao, Z.; Cahir, C.; Giani, A. M.; Li, Y.; Dong, X.; Moroziewicz, D.; The NYSCF Global Stem Cell Array® Team; Paull, D.; Chen, Z.; Zhong, A.; Noggle, S. A.; Rice, C. M.; Qi, Q.; Evans, T.; Chen, S. |
| Article Title: | Isogenic human trophectoderm cells demonstrate the role of NDUFA4 and associated variants in ZIKV infection |
| Abstract: | Population-based genome-wide association studies (GWAS) normally require a large sample size, which can be labor intensive and costly. Recently, we reported a human induced pluripotent stem cell (hiPSC) array-based GWAS method, identifying NDUFA4 as a host factor for Zika virus (ZIKV) infection. In this study, we extended our analysis to trophectoderm cells, which constitute one of the major routes of mother-to-fetus transmission of ZIKV during pregnancy. We differentiated hiPSCs from various donors into trophectoderm cells. We then infected cells carrying loss of function mutations in NDUFA4, harboring risk versus non-risk alleles of SNPs (rs917172 and rs12386620) or having deletions in the NDUFA4 cis-regulatory region with ZIKV. We found that loss/reduction of NDUFA4 suppressed ZIKV infection in trophectoderm cells. This study validated our published hiPSC array-based system as a useful platform for GWAS and confirmed the role of NDUFA4 as a susceptibility locus for ZIKV in disease-relevant trophectoderm cells. © 2023 The Author(s) |
| Keywords: | virology; stem cells research |
| Journal Title: | iScience |
| Volume: | 26 |
| Issue: | 7 |
| ISSN: | 2589-0042 |
| Publisher: | Cell Press |
| Date Published: | 2023-07-21 |
| Start Page: | 107001 |
| Language: | English |
| DOI: | 10.1016/j.isci.2023.107001 |
| PROVIDER: | scopus |
| PMCID: | PMC10391681 |
| PUBMED: | 37534130 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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