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NF-κB inhibitor alpha has a cross-variant role during SARS-CoV-2 infection in ACE2-overexpressing human airway organoids.

التفاصيل البيبلوغرافية
العنوان: NF-κB inhibitor alpha has a cross-variant role during SARS-CoV-2 infection in ACE2-overexpressing human airway organoids.
المؤلفون: Simoneau CR; Gladstone Institute of Virology, San Francisco, CA, USA.; Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, CA, USA., Chen PY; Gladstone Institute of Virology, San Francisco, CA, USA., Xing GK; Chan-Zuckerberg Biohub, San Francisco, CA, USA.; Center for Computational Biology, University of California, Berkeley, Berkeley CA, USA., Khalid MM; Gladstone Institute of Virology, San Francisco, CA, USA., Meyers NL; Gladstone Institute of Virology, San Francisco, CA, USA., Hayashi JM; Gladstone Institute of Virology, San Francisco, CA, USA., Taha TY; Gladstone Institute of Virology, San Francisco, CA, USA., Leon KE; Gladstone Institute of Virology, San Francisco, CA, USA.; Medical Scientist Training Program, University of California San Francisco, San Francisco, CA, USA., Ashuach T; Center for Computational Biology, University of California, Berkeley, Berkeley CA, USA., Fontaine KA; Gladstone Institute of Virology, San Francisco, CA, USA., Rodriguez L; ImmunoX CoLabs, University of California San Francisco, San Francisco, CA, USA., Joehnk B; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA., Walcott K; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA., Vasudevan S; Medical Service, San Francisco VA Healthcare System, San Francisco, CA, USA., Fang X; Department of Medicine and Department of Anesthesia, Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA., Maishan M; Department of Medicine and Department of Anesthesia, Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA., Schultz S; Center for Computational Biology, University of California, Berkeley, Berkeley CA, USA., Roose J; Department of Anatomy, University of California San Francisco, San Francisco, CA, USA., Matthay MA; Department of Medicine and Department of Anesthesia, Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA., Sil A; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA., Arjomandi M; Medical Service, San Francisco VA Healthcare System, San Francisco, CA, USA.; Division of Pulmonary and Critical Care, Department of Medicine, University of California San Francisco, San Francisco, CA, USA., Yosef N; Center for Computational Biology, University of California, Berkeley, Berkeley CA, USA.; Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel., Ott M; Gladstone Institute of Virology, San Francisco, CA, USA.; Chan-Zuckerberg Biohub, San Francisco, CA, USA.; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
المصدر: BioRxiv : the preprint server for biology [bioRxiv] 2022 Aug 02. Date of Electronic Publication: 2022 Aug 02.
نوع المنشور: Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
مستخلص: As SARS-CoV-2 continues to spread worldwide, tractable primary airway cell models that accurately recapitulate the cell-intrinsic response to arising viral variants are needed. Here we describe an adult stem cell-derived human airway organoid model overexpressing the ACE2 receptor that supports robust viral replication while maintaining 3D architecture and cellular diversity of the airway epithelium. ACE2-OE organoids were infected with SARS-CoV-2 variants and subjected to single-cell RNA-sequencing. NF-κB inhibitor alpha was consistently upregulated in infected epithelial cells, and its mRNA expression positively correlated with infection levels. Confocal microscopy showed more IκBα expression in infected than bystander cells, but found concurrent nuclear translocation of NF-κB that IκBα usually prevents. Overexpressing a nondegradable IκBα mutant reduced NF-κB translocation and increased viral infection. These data demonstrate the functionality of ACE2-OE organoids in SARS-CoV-2 research and identify an incomplete NF-κB feedback loop as a rheostat of viral infection that may promote inflammation and severe disease.
التعليقات: Update in: Sci Rep. 2024 Jul 4;14(1):15351. doi: 10.1038/s41598-024-66003-2. (PMID: 38961189)
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معلومات مُعتمدة: P01 AI091580 United States AI NIAID NIH HHS; T32 AI060537 United States AI NIAID NIH HHS; U19 AI135990 United States AI NIAID NIH HHS
تواريخ الأحداث: Date Created: 20220819 Latest Revision: 20240715
رمز التحديث: 20240715
مُعرف محوري في PubMed: PMC9387123
DOI: 10.1101/2022.08.02.502100
PMID: 35982664
قاعدة البيانات: MEDLINE
الوصف
تدمد:2692-8205
DOI:10.1101/2022.08.02.502100