A human iPSC-array-based GWAS identifies a virus susceptibility locus in the NDUFA4 gene and functional variants.

Humans Alleles COVID-19 / genetics DNA, Mitochondrial / metabolism Electron Transport Complex IV / genetics Genetic Predisposition to Disease Genome-Wide Association Study Induced Pluripotent Stem Cells / metabolism Interferon Type I / metabolism Polymorphism, Single Nucleotide SARS-CoV-2 Zika Virus Zika Virus Infection / genetics Dengue / genetics
Dengue Virus NDUFA4 SARS-CoV-2 genome-wide association study iPSC array isogenic hiPSC lines mtDNA risk allele single-nucleotide polymorphism type I interferon

Journal

Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472

Informations de publication

Date de publication:
06 10 2022
Historique:
received: 25 09 2021
revised: 09 06 2022
accepted: 16 09 2022
pubmed: 8 10 2022
medline: 12 10 2022
entrez: 7 10 2022
Statut: ppublish

Résumé

Population-based studies to identify disease-associated risk alleles typically require samples from a large number of individuals. Here, we report a human-induced pluripotent stem cell (hiPSC)-based screening strategy to link human genetics with viral infectivity. A genome-wide association study (GWAS) identified a cluster of single-nucleotide polymorphisms (SNPs) in a cis-regulatory region of the NDUFA4 gene, which was associated with susceptibility to Zika virus (ZIKV) infection. Loss of NDUFA4 led to decreased sensitivity to ZIKV, dengue virus, and SARS-CoV-2 infection. Isogenic hiPSC lines carrying non-risk alleles of SNPs or deletion of the cis-regulatory region lower sensitivity to viral infection. Mechanistic studies indicated that loss/reduction of NDUFA4 causes mitochondrial stress, which leads to the leakage of mtDNA and thereby upregulation of type I interferon signaling. This study provides proof-of-principle for the application of iPSC arrays in GWAS and identifies NDUFA4 as a previously unknown susceptibility locus for viral infection.

Identifiants

DOI: 10.1016/j.stem.2022.09.008 PMID: 36206731 PMC: PMC9550219
pubmed: 36206731
pii: S1934-5909(22)00385-X
doi: 10.1016/j.stem.2022.09.008
pmc: PMC9550219
pii:
doi:

Substances chimiques

DNA, Mitochondrial 0
Electron Transport Complex IV EC 1.9.3.1
Interferon Type I 0
NDUFA4 protein, human EC 1.9.3.1

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1475-1490.e6

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK116075
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK124463
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI124690
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI091707
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK127777
Pays : United States
Organisme : NICHD NIH HHS
ID : F32 HD096810
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK130454
Pays : United States
Organisme : NIDDK NIH HHS
ID : DP3 DK111907
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK119667
Pays : United States

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests R.E.S. is on the scientific advisory board of Miromatrix, Inc and Lime Therapeutics and is a paid consultant and speaker for Alnylam, Inc. S.C. and T.E. are the co-founders of OncoBeat, LLC. S.C. is a consultant of Vesaliustx Therapeutics.

Références

Mol Biol Cell. 2014 Jan;25(1):76-86
pubmed: 24173717
Nature. 2021 Mar;591(7848):92-98
pubmed: 33307546
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
Nature. 2021 Dec;600(7889):472-477
pubmed: 34237774
Cell Stem Cell. 2020 Jul 2;27(1):125-136.e7
pubmed: 32579880
Cell. 2020 May 28;181(5):1036-1045.e9
pubmed: 32416070
J Cell Biol. 2017 Jul 3;216(7):2027-2045
pubmed: 28566324
J Cell Biochem. 2012 Oct;113(10):3061-8
pubmed: 22573568
Nat Methods. 2015 Sep;12(9):885-92
pubmed: 26237226
Cell Host Microbe. 2018 Aug 8;24(2):308-323.e6
pubmed: 30092202
Trends Endocrinol Metab. 2017 Nov;28(11):761-770
pubmed: 28988874
N Engl J Med. 2016 Mar 10;374(10):951-8
pubmed: 26862926
N Engl J Med. 2020 Oct 15;383(16):1522-1534
pubmed: 32558485
Nature. 2015 Apr 23;520(7548):553-7
pubmed: 25642965
Cell Stem Cell. 2017 Oct 5;21(4):472-488.e10
pubmed: 28965766
Cell Stem Cell. 2017 Aug 3;21(2):274-283.e5
pubmed: 28736217
Am J Cancer Res. 2015 Aug 15;5(9):2816-22
pubmed: 26609487
Mol Neurodegener. 2011 Jul 26;6(1):53
pubmed: 21791084
Cell Res. 2018 Oct;28(10):1026-1034
pubmed: 30030519
Sci Rep. 2018 Nov 26;8(1):17384
pubmed: 30478404
Genes Immun. 2013 Jan;14(1):52-7
pubmed: 23151486
Nat Cell Biol. 2022 Jan;24(1):24-34
pubmed: 35027731
Toxicol Sci. 2008 Jan;101(1):101-11
pubmed: 17906319
Dis Model Mech. 2018 Nov 20;11(11):
pubmed: 30361421
Nat Biotechnol. 2019 Aug;37(8):907-915
pubmed: 31375807
J Clin Invest. 2018 Oct 1;128(10):4697-4710
pubmed: 30063220
Cell. 2020 May 28;181(5):1016-1035.e19
pubmed: 32413319
Cell. 2017 May 04;169(4):597-609.e11
pubmed: 28475892
Nature. 2015 Aug 27;524(7566):471-5
pubmed: 26266980
PLoS One. 2017 Apr 28;12(4):e0176795
pubmed: 28453550
BMC Med Genet. 2012 Dec 19;13:123
pubmed: 23253088
Nature. 2020 Nov;587(7835):610-612
pubmed: 32998156
Cell Stem Cell. 2017 Mar 2;20(3):397-406.e5
pubmed: 28132835
Infect Genet Evol. 2018 Dec;66:286-307
pubmed: 28951201
Cell Metab. 2012 Sep 5;16(3):378-86
pubmed: 22902835
J Virol. 2021 Nov 9;95(23):e0125721
pubmed: 34523966
Cell Stem Cell. 2016 May 5;18(5):587-90
pubmed: 26952870
Nucleic Acids Res. 2019 May 7;47(8):e47
pubmed: 30783653
Nat Commun. 2018 May 29;9(1):2090
pubmed: 29844387
Cell. 2016 May 19;165(5):1238-1254
pubmed: 27118425
Nat Genet. 2010 Jul;42(7):558-60
pubmed: 20581876
Nat Rev Immunol. 2011 Jun;11(6):389-402
pubmed: 21597473
Cell Rep. 2013 Jun 27;3(6):1795-805
pubmed: 23746447
Cell Rep. 2021 Nov 9;37(6):109920
pubmed: 34731648
Cell Host Microbe. 2020 Jun 10;27(6):883-890.e2
pubmed: 32407669
Nature. 2021 Jan;589(7841):270-275
pubmed: 33116299
BMC Infect Dis. 2021 Jul 16;21(1):688
pubmed: 34271860
Cell. 2013 Sep 26;155(1):242-56
pubmed: 24074872
Cell. 2015 Apr 9;161(2):387-403
pubmed: 25772697
Mitochondrion. 2007 Jul;7(4):284-7
pubmed: 17395552
Nature. 2010 Mar 4;464(7285):104-7
pubmed: 20203610
J Neurosci. 2017 Feb 22;37(8):2161-2175
pubmed: 28123079

Auteurs

Yuling Han (Y)

Department of Surgery, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.

Lei Tan (L)

Department of Surgery, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA; Center for Energy Metabolism and Reproduction, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

Ting Zhou (T)

Department of Surgery, Weill Cornell Medical College, 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.

Liuliu Yang (L)

Department of Surgery, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.

Lucia Carrau (L)

Department of Microbiology, New York University, 430 E 29th Street, New York, NY 10016, USA.

Lauretta A Lacko (LA)

Department of Surgery, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.

Mohsan Saeed (M)

Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA; National Emerging Infectious Diseases Laboratories (NEIDL), Boston University, Boston, MA 02118, USA.

Jiajun Zhu (J)

Department of Surgery, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.

Zeping Zhao (Z)

Department of Surgery, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.

Benjamin E Nilsson-Payant (BE)

Department of Microbiology, New York University, 430 E 29th Street, New York, NY 10016, USA.

Filipe Tenorio Lira Neto (FT)

Department of Urology, Instituto de Medicina Integral Prof. Fernando Figueira, Recife, Brazil.

Clare Cahir (C)

Department of Surgery, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA; The Tri-Institutional PhD Program in Chemical Biology, New York, NY, USA.

Alice Maria Giani (AM)

Department of Surgery, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.

Jin Chou Chai (JC)

Department of Epidemiology & Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.

Yang Li (Y)

Department of Epidemiology & Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.

Xue Dong (X)

Department of Surgery, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.

Dorota Moroziewicz (D)

The New York Stem Cell Foundation Research Institute, 619 West 54th Street, 3rd Floor, New York, NY 10019, USA.
The New York Stem Cell Foundation Research Institute, 619 West 54th Street, 3rd Floor, New York, NY 10019, USA.

Daniel Paull (D)

The New York Stem Cell Foundation Research Institute, 619 West 54th Street, 3rd Floor, New York, NY 10019, USA.

Tuo Zhang (T)

Genomic Resource Core Facility, Weill Cornell Medical College, New York, NY 10065, USA.

Soyeon Koo (S)

Department of Surgery, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA; Weill Cornell Neuroscience PhD Program, New York, NY, USA.

Christina Tan (C)

Department of Surgery, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.

Ron Danziger (R)

Department of Surgery, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.

Qian Ba (Q)

Department of Surgery, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA; School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Lingling Feng (L)

Department of Surgery, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA; Key Laboratory of Pesticide and Chemical Biology (CCNU), Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, Hubei 430079, China.

Zhengming Chen (Z)

Department of Population Health Sciences, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.

Aaron Zhong (A)

Stem Cell Research Facility, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.

Gilbert J Wise (GJ)

Department of Urology, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.

Jenny Z Xiang (JZ)

Genomic Resource Core Facility, Weill Cornell Medical College, New York, NY 10065, USA.

Hui Wang (H)

School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Robert E Schwartz (RE)

Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.

Benjamin R tenOever (BR)

Department of Microbiology, New York University, 430 E 29th Street, New York, NY 10016, USA.

Scott A Noggle (SA)

The New York Stem Cell Foundation Research Institute, 619 West 54th Street, 3rd Floor, New York, NY 10019, USA.

Charles M Rice (CM)

Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.

Qibin Qi (Q)

Department of Epidemiology & Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.

Todd Evans (T)

Department of Surgery, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.

Shuibing Chen (S)

Department of Surgery, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA. Electronic address: shc2034@med.cornell.edu.

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