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Common Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection.
- Source :
-
Stem cell reports [Stem Cell Reports] 2021 Mar 09; Vol. 16 (3), pp. 505-518. Date of Electronic Publication: 2021 Feb 13. - Publication Year :
- 2021
-
Abstract
- 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.<br /> (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- 3' Untranslated Regions genetics
Adolescent
Adult
Animals
COVID-19 virology
Cell Line
Chlorocebus aethiops
Clustered Regularly Interspaced Short Palindromic Repeats genetics
Female
Furin genetics
Host-Pathogen Interactions genetics
Humans
Induced Pluripotent Stem Cells virology
Male
Neurons virology
Peptide Hydrolases genetics
SARS-CoV-2 pathogenicity
Vero Cells
COVID-19 genetics
Genetic Predisposition to Disease genetics
Polymorphism, Single Nucleotide genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2213-6711
- Volume :
- 16
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Stem cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 33636110
- Full Text :
- https://doi.org/10.1016/j.stemcr.2021.02.010