Common Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection.
Publication/Presentation Date
3-9-2021
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.
Volume
16
Issue
3
First Page
505
Last Page
518
ISSN
2213-6711
Published In/Presented At
Dobrindt, K., Hoagland, D. A., Seah, C., Kassim, B., O'Shea, C. P., Murphy, A., Iskhakova, M., Fernando, M. B., Powell, S. K., Deans, P. J. M., Javidfar, B., Peter, C., Møller, R., Uhl, S. A., Garcia, M. F., Kimura, M., Iwasawa, K., Crary, J. F., Kotton, D. N., Takebe, T., … Brennand, K. J. (2021). Common Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection. Stem cell reports, 16(3), 505–518. https://doi.org/10.1016/j.stemcr.2021.02.010
Disciplines
Medicine and Health Sciences
PubMedID
33636110
Department(s)
Medical Education
Document Type
Article