Isogenic human trophectoderm cells demonstrate the role of NDUFA4 and associated variants in ZIKV infection

  • iScience. 2023 May 29;26(7):107001. doi: 10.1016/j.isci.2023.107001.
Liuliu Yang  1  2 ,  Yuling Han  1  2 ,  Ting Zhou  1  3 ,  Lauretta A Lacko  1 ,  Mohsan Saeed  4  5  6 ,  Christina Tan  1 ,  Ron Danziger  1 ,  Jiajun Zhu  1  2 ,  Zeping Zhao  1  2 ,  Clare Cahir  1 ,  Alice Maria Giani  1 ,  Yang Li  7 ,  Xue Dong  1 ,  Dorota Moroziewicz  8 ,  NYSCF Global Stem Cell Array® Team ,  Daniel Paull  8 ,  Zhengming Chen  9 ,  Aaron Zhong  3 ,  Scott A Noggle  8 ,  Charles M Rice  4 ,  Qibin Qi  7 ,  Todd Evans  1  2 ,  Shuibing Chen  1  2
Affiliations
  • 1. Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • 2. Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • 3. Stem Cell Research Facility, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
  • 4. Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
  • 5. Department of Biochemistry & Cell Biology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA.
  • 6. National Emerging Infectious Diseases Laboratories (NEIDL), Boston University, Boston, MA 02118, USA.
  • 7. Department of Epidemiology & Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
  • 8. The New York Stem Cell Foundation Research Institute, 619 West 54th Street, 3Road Floor, New York, NY 10019, USA.
  • 9. Department of Population Health Sciences, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
PMID: 37534130 DOI: 10.1016/j.isci.2023.107001
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.

Keywords
Stem cells research; Virology.
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