Common genetic variation in humans impacts in vitro susceptibility to SARS-CoV-2 infection.

Autor:	Dobrindt K; Pamela Sklar Division of Psychiatric Genomics, Department of Genetics and Genomics, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Hoagland DA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY 10029, USA.; Graduate School of Biomedical Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Seah C; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Graduate School of Biomedical Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Kassim B; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029., O'Shea CP; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Iskhakova M; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Fernando MB; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Graduate School of Biomedical Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Deans PJM; Pamela Sklar Division of Psychiatric Genomics, Department of Genetics and Genomics, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Powell SK; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Graduate School of Biomedical Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Javidfar B; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Murphy A; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Graduate School of Biomedical Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Peter C; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Møeller R; Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY 10029, USA.; Graduate School of Biomedical Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Garcia MF; Pamela Sklar Division of Psychiatric Genomics, Department of Genetics and Genomics, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Kimura M; Division of Gastroenterology, Hepatology and Nutrition; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center; Center for Stem Cell and Organoid Medicine (CuSTOM); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States; Institute of Research, Tokyo Medical and Dental University (TMDU), Tokyo, Japan., Iwasawa K; Division of Gastroenterology, Hepatology and Nutrition; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center; Center for Stem Cell and Organoid Medicine (CuSTOM); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States; Institute of Research, Tokyo Medical and Dental University (TMDU), Tokyo, Japan., Crary J; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Kotton DN; Center for Regenerative Medicine of Boston University and Boston Medical Center, Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA., Takebe T; Division of Gastroenterology, Hepatology and Nutrition; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center; Center for Stem Cell and Organoid Medicine (CuSTOM); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States; Institute of Research, Tokyo Medical and Dental University (TMDU), Tokyo, Japan., Huckins LM; Pamela Sklar Division of Psychiatric Genomics, Department of Genetics and Genomics, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Mental Illness Research, Education and Clinical Centers, James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY 10468, USA., tenOever BR; Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY 10029, USA., Akbarian S; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Brennand KJ; Pamela Sklar Division of Psychiatric Genomics, Department of Genetics and Genomics, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2020 Sep 21. Date of Electronic Publication: 2020 Sep 21.
DOI:	10.1101/2020.09.20.300574
Abstrakt:	The host response to SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, demonstrates significant inter-individual variability. In addition to showing more disease in males, the elderly, and individuals with underlying comorbidities, SARS-CoV-2 can seemingly render healthy individuals with profound clinical complications. We hypothesize that, in addition to viral load and host antibody repertoire, host genetic variants also impact 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 at large, and located in the 3'UTR of the protease FURIN, impacts alveolar and neuron infection by SARS-CoV-2 in vitro . Thus, we provide a proof-of-principle finding that common genetic variation can impact viral infection, and thus contribute to clinical heterogeneity in SARS-CoV-2. Ongoing genetic studies will help to better identify high-risk individuals, predict clinical complications, and facilitate the discovery of drugs that might treat disease. Competing Interests: CONFLICT OF INTEREST STATEMENT The authors declare no conflicts of interest.
Databáze:	MEDLINE
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