Isogenic human trophectoderm cells demonstrate the role of NDUFA4 and associated variants in ZIKV infection
Liuliu Yang,
Yuling Han,
Ting Zhou,
Lauretta A. Lacko,
Mohsan Saeed,
Christina Tan,
Ron Danziger,
Jiajun Zhu,
Zeping Zhao,
Clare Cahir,
Alice Maria Giani,
Yang Li,
Xue Dong,
Dorota Moroziewicz,
Daniel Paull,
Zhengming Chen,
Aaron Zhong,
Scott A. Noggle,
Charles M. Rice,
Qibin Qi,
Todd Evans,
Shuibing Chen
Affiliations
Liuliu Yang
Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Yuling Han
Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Ting Zhou
Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Stem Cell Research Facility, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
Lauretta A. Lacko
Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Mohsan Saeed
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA; Department of Biochemistry & Cell Biology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA; National Emerging Infectious Diseases Laboratories (NEIDL), Boston University, Boston, MA 02118, USA
Christina Tan
Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Ron Danziger
Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Jiajun Zhu
Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Zeping Zhao
Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Clare Cahir
Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Alice Maria Giani
Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Yang Li
Department of Epidemiology & Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
Xue Dong
Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Dorota Moroziewicz
The New York Stem Cell Foundation Research Institute, 619 West 54th Street, 3Road Floor, New York, NY 10019, USA
Daniel Paull
The New York Stem Cell Foundation Research Institute, 619 West 54th Street, 3Road Floor, New York, NY 10019, USA
Zhengming Chen
Department of Population Health Sciences, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Aaron Zhong
Stem Cell Research Facility, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
Scott A. Noggle
The New York Stem Cell Foundation Research Institute, 619 West 54th Street, 3Road Floor, New York, NY 10019, USA
Charles M. Rice
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA
Qibin Qi
Department of Epidemiology & Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
Todd Evans
Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Shuibing Chen
Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Corresponding author
Summary: 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.
