Evidence map›Paper›PMID 35982664›Full record

ArticlebioRxiv : the preprint server for biology2022

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

Camille R Simoneau, Pei-Yi Chen, Galen K Xing, Mir M Khalid, Nathan L Meyers, Jennifer M Hayashi, Taha Y Taha, Kristoffer E Leon, Tal Ashuach, Krystal A Fontaine and 13 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 3 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 6 institutions in 2 countries.

Camille R SimoneauGladstone Institute of Virology, San Francisco, CA, USA.
Pei-Yi ChenGladstone Institute of Virology, San Francisco, CA, USA.
Galen K XingChan-Zuckerberg Biohub, San Francisco, CA, USA.
Mir M KhalidGladstone Institute of Virology, San Francisco, CA, USA.
Nathan L MeyersGladstone Institute of Virology, San Francisco, CA, USA.
Jennifer M HayashiGladstone Institute of Virology, San Francisco, CA, USA.
Taha Y TahaGladstone Institute of Virology, San Francisco, CA, USA.
Kristoffer E LeonGladstone Institute of Virology, San Francisco, CA, USA.
Tal AshuachCenter for Computational Biology, University of California, Berkeley, Berkeley CA, USA.
Krystal A FontaineGladstone Institute of Virology, San Francisco, CA, USA.
Lauren RodriguezImmunoX CoLabs, University of California San Francisco, San Francisco, CA, USA.
Bastian JoehnkDepartment of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA.
Keith WalcottDepartment of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA.
Sreelakshmi VasudevanMedical Service, San Francisco VA Healthcare System, San Francisco, CA, USA.
Xiaohui FangDepartment of Medicine and Department of Anesthesia, Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA.
Mazharul MaishanDepartment of Medicine and Department of Anesthesia, Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA.
Shawn SchultzCenter for Computational Biology, University of California, Berkeley, Berkeley CA, USA.
Jeroen RooseDepartment of Anatomy, University of California San Francisco, San Francisco, CA, USA.
Michael A MatthayDepartment of Medicine and Department of Anesthesia, Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA.
Anita SilDepartment of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA.
Mehrdad ArjomandiMedical Service, San Francisco VA Healthcare System, San Francisco, CA, USA.
Nir YosefCenter for Computational Biology, University of California, Berkeley, Berkeley CA, USA.
Melanie OttGladstone Institute of Virology, San Francisco, CA, USA.
Gladstone Institutes · USUniversity of California, San Francisco · USUniversity of California, Berkeley · USChan Zuckerberg Initiative (United States) · USSan Francisco VA Health Care System · USWeizmann Institute of Science · IL

Funding

Understand the metabolic fitness of naïve T cellsP01AI091580 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JEROEN ROOSE · 2011 to 2026
$31.1M
RESEARCH PROJECT 2U19AI135990 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nevan J Krogan · 2018 to 2026
$21.4M
Microbial Pathogenesis and Host DefenseT32AI060537 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joanne N. Engel · 2004 to 2026
$6.5M
NIAID NIH HHS P01 AI091580NIAID NIH HHS T32 AI060537NIAID NIH HHS U19 AI135990
6 · The paper itself

Abstract

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.

Identifiers

PMID35982664
PMCPMC9387123
OpenAlexW4289522464

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.