Common Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection
| Autor: | John F. Crary, Samuel K. Powell, Benjamin R. tenOever, Carina Seah, Cyril J. Peter, Ben Javidfar, Skyler Uhl, Kristina Dobrindt, Kentaro Iwasawa, Rasmus Møller, Laura M. Huckins, Michael B. Fernando, Meilin Fernandez Garcia, Callan O’Shea, P J Michael Deans, Takanori Takebe, Aleta Murphy, Marina Iskhakova, Schahram Akbarian, Bibi Kassim, Daisy A. Hoagland, Kristen J. Brennand, Masaki Kimura, Darrell N. Kotton |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine Untranslated region Adolescent viruses brain Induced Pluripotent Stem Cells Population neurons Disease Biology Polymorphism Single Nucleotide Biochemistry Article Cell Line FURIN rs4702 03 medical and health sciences 0302 clinical medicine Chlorocebus aethiops Genetic variation Genetics Animals Humans CRISPR Clustered Regularly Interspaced Short Palindromic Repeats Genetic Predisposition to Disease education Induced pluripotent stem cell 3' Untranslated Regions Vero Cells Furin education.field_of_study SARS-CoV-2 fungi human induced pluripotent stem cell COVID-19 Cell Biology 030104 developmental biology host genetics Host-Pathogen Interactions biology.protein Female Viral load 030217 neurology & neurosurgery Peptide Hydrolases Developmental Biology |
| Zdroj: | Stem Cell Reports bioRxiv |
| ISSN: | 2213-6711 |
| DOI: | 10.1016/j.stemcr.2021.02.010 |
| Popis: | 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. Graphical abstract Brennand, Akbarian, and colleagues combine human induced pluripotent stem cell-based models and CRISPR engineering to explore the host genetics of SARS-CoV-2 in alveolar cells, intestinal cells, and neurons. A SNP(rs4702) located in the 3′ UTR of the protease FURIN influences alveolar and neuron infection by SARS-CoV-2 in vitro. |
| Databáze: | OpenAIRE |
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