دورية أكاديمية
أعرض في EDS

Systematic functional interrogation of SARS-CoV-2 host factors using Perturb-seq.

التفاصيل البيبلوغرافية
العنوان: Systematic functional interrogation of SARS-CoV-2 host factors using Perturb-seq.
المؤلفون: Sunshine S; Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA., Puschnik AS; Chan Zuckerberg Biohub, San Francisco, San Francisco, CA, USA., Replogle JM; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.; Whitehead Institute for Biomedical Research, Cambridge, MA, USA., Laurie MT; Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA., Liu J; Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA.; University of California, Berkeley-UCSF Joint Graduate Program in Bioengineering, San Francisco, CA, USA., Zha BS; Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, San Francisco, CA, USA., Nuñez JK; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.; Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, CA, USA., Byrum JR; Chan Zuckerberg Biohub, San Francisco, San Francisco, CA, USA., McMorrow AH; Chan Zuckerberg Biohub, San Francisco, San Francisco, CA, USA., Frieman MB; Department of Microbiology and Immunology, Center for Pathogen Research, University of Maryland School of Medicine, Baltimore, MD, USA., Winkler J; Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA, USA.; Center for Cancer Research, Medical University of Vienna, Vienna, Austria., Qiu X; Whitehead Institute for Biomedical Research, Cambridge, MA, USA.; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA., Rosenberg OS; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA., Leonetti MD; Chan Zuckerberg Biohub, San Francisco, San Francisco, CA, USA., Ye CJ; Division of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.; Institute of Human Genetics, University of California San Francisco, San Francisco, CA, USA.; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA.; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA., Weissman JS; Whitehead Institute for Biomedical Research, Cambridge, MA, USA. weissman@wi.mit.edu.; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA. weissman@wi.mit.edu.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. weissman@wi.mit.edu.; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. weissman@wi.mit.edu., DeRisi JL; Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA. joe@derisilab.ucsf.edu.; Chan Zuckerberg Biohub, San Francisco, San Francisco, CA, USA. joe@derisilab.ucsf.edu., Hein MY; Chan Zuckerberg Biohub, San Francisco, San Francisco, CA, USA. marco.hein@maxperutzlabs.ac.at.; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA. marco.hein@maxperutzlabs.ac.at.; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA. marco.hein@maxperutzlabs.ac.at.; Max Perutz Labs, Vienna Biocenter Campus (VBC), Vienna, Austria. marco.hein@maxperutzlabs.ac.at.; Medical University of Vienna, Center for Medical Biochemistry, Vienna, Austria. marco.hein@maxperutzlabs.ac.at.
المصدر: Nature communications [Nat Commun] 2023 Oct 06; Vol. 14 (1), pp. 6245. Date of Electronic Publication: 2023 Oct 06.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: SARS-CoV-2*/genetics , COVID-19*/genetics, Humans ; Proteomics ; Lung ; Epithelial Cells
مستخلص: Genomic and proteomic screens have identified numerous host factors of SARS-CoV-2, but efficient delineation of their molecular roles during infection remains a challenge. Here we use Perturb-seq, combining genetic perturbations with a single-cell readout, to investigate how inactivation of host factors changes the course of SARS-CoV-2 infection and the host response in human lung epithelial cells. Our high-dimensional data resolve complex phenotypes such as shifts in the stages of infection and modulations of the interferon response. However, only a small percentage of host factors showed such phenotypes upon perturbation. We further identified the NF-κB inhibitor IκBα (NFKBIA), as well as the translation factors EIF4E2 and EIF4H as strong host dependency factors acting early in infection. Overall, our study provides massively parallel functional characterization of host factors of SARS-CoV-2 and quantitatively defines their roles both in virus-infected and bystander cells.
(© 2023. Springer Nature Limited.)
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معلومات مُعتمدة: F31 AI150007 United States AI NIAID NIH HHS
تواريخ الأحداث: Date Created: 20231006 Date Completed: 20231101 Latest Revision: 20240210
رمز التحديث: 20240210
مُعرف محوري في PubMed: PMC10558542
DOI: 10.1038/s41467-023-41788-4
PMID: 37803001
قاعدة البيانات: MEDLINE
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