| Title | Isogenic human trophectoderm cells demonstrate the role of NDUFA4 and associated variants in ZIKV infection. |
| Publication Type | Journal Article |
| Year of Publication | 2023 |
| Authors | Yang, L, Han, Y, Zhou, T, Lacko, LA, Saeed, M, Tan, C, Danziger, R, Zhu, J, Zhao, Z, Cahir, C, Giani, AMaria, Li, Y, Dong, X, Moroziewicz, D, Paull, D, Chen, Z, Zhong, A, Noggle, SA, Rice, CM, Qi, Q, Evans, T, Chen, S |
| Corporate Authors | |
| Journal | iScience |
| Volume | 26 |
| Issue | 7 |
| Pagination | 107001 |
| Date Published | 2023 Jul 21 |
| ISSN | 2589-0042 |
| 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. |
| DOI | 10.1016/j.isci.2023.107001 |
| Alternate Journal | iScience |
| PubMed ID | 37534130 |
| PubMed Central ID | PMC10391681 |