Common Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection.
3' Untranslated Regions
/ genetics
Adolescent
Adult
Animals
COVID-19
/ genetics
Cell Line
Chlorocebus aethiops
Clustered Regularly Interspaced Short Palindromic Repeats
/ genetics
Female
Furin
/ genetics
Genetic Predisposition to Disease
/ genetics
Host-Pathogen Interactions
/ genetics
Humans
Induced Pluripotent Stem Cells
/ virology
Male
Neurons
/ virology
Peptide Hydrolases
/ genetics
Polymorphism, Single Nucleotide
/ genetics
SARS-CoV-2
/ pathogenicity
Vero Cells
FURIN rs4702
SARS-CoV-2
brain
host genetics
human induced pluripotent stem cell
neurons
Journal
Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300
Informations de publication
Date de publication:
09 03 2021
09 03 2021
Historique:
received:
25
09
2020
revised:
09
02
2021
accepted:
10
02
2021
pubmed:
27
2
2021
medline:
25
3
2021
entrez:
26
2
2021
Statut:
ppublish
Résumé
The host response to SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, demonstrates significant interindividual variability. In addition to showing more disease in males, the elderly, and individuals with underlying comorbidities, SARS-CoV-2 can seemingly afflict healthy individuals with profound clinical complications. We hypothesize that, in addition to viral load and host antibody repertoire, host genetic variants influence vulnerability to infection. Here we apply human induced pluripotent stem cell (hiPSC)-based models and CRISPR engineering to explore the host genetics of SARS-CoV-2. We demonstrate that a single-nucleotide polymorphism (rs4702), common in the population and located in the 3' UTR of the protease FURIN, influences alveolar and neuron infection by SARS-CoV-2 in vitro. Thus, we provide a proof-of-principle finding that common genetic variation can have an impact on viral infection and thus contribute to clinical heterogeneity in COVID-19. Ongoing genetic studies will help to identify high-risk individuals, predict clinical complications, and facilitate the discovery of drugs.
Identifiants
pubmed: 33636110
pii: S2213-6711(21)00090-4
doi: 10.1016/j.stemcr.2021.02.010
pmc: PMC7881728
pii:
doi:
Substances chimiques
3' Untranslated Regions
0
Peptide Hydrolases
EC 3.4.-
Furin
EC 3.4.21.75
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
505-518Subventions
Organisme : NIDDK NIH HHS
ID : UG3 DK119982
Pays : United States
Organisme : NICHD NIH HHS
ID : P01 HD093363
Pays : United States
Organisme : NIDDK NIH HHS
ID : UH3 DK119982
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA048279
Pays : United States
Organisme : NIDDK NIH HHS
ID : DP2 DK128799
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
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