ArticleCell2020
SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract.
Open access · bronzeAbstract read
In one paragraph
Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,016 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
1,016citing papers in PubMed, 1 pooled it
196.6field-weighted citation impact, top 1% of its field
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.
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.
Who cites it
1,016 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,643 citations in OpenAlex.
- Washing Illness Away: A Systematic Review of the Impact of Nasal Irrigation and Spray on COVID-19.The Laryngoscope · 2025Pooled it
- Azelastine Nasal Spray for Prevention of SARS-CoV-2 Infections: A Phase 2 Randomized Clinical Trial.JAMA internal medicine · 2025Trial
- Safety, pharmacokinetics, and pharmacodynamics of human interferon-α2b spray in healthy participants.Antimicrobial agents and chemotherapy · 2025Trial
- Chimeric SARS-CoV-2 vaccine vectors stably incorporating the functional glycoprotein of VSV.iScience · 2026Article
- Exposure route, not dose, is the primary driver of infection patterns for a respiratory virus.Science advances · 2026Article
- Article
- Selective decay of interferon mRNAs controls antiviral immunity and innate memory.Molecular cell · 2026Article
- SARS-CoV-2 infection produces an IL-33-dependent chronic eosinophilic pneumonia and muco-inflammatory airways disease in Scnn1b-Tg mice.JCI insight · 2026Article
- Coronavirus membrane protein with a fluorescent protein tag enables particle tracking for the study of virus assembly and egress in live cells.Journal of virology · 2026Article
- Nicotine and cotinine enhance SARS-CoV-2 entry through distinct but complementary mechanisms in human respiratory epithelial cells.Journal of virology · 2026Article
- Structural and functional characterization of a conserved cryptic epitope on SARS-CoV-2 spike S2 subunit.PLoS pathogens · 2026Article
- An immune-poised state of human bronchial epithelial cells mediates defense against RSV in adults.Nature communications · 2026Article
- Double trouble: how co- and superinfections shape viral dynamics and host responses.Journal of virology · 2026Review
- The Gut-Lung Microbiome Axis in Alveolar Stem Cell Regeneration and Lung Repair.Microorganisms · 2026Review
- Temporal Dynamics of Innate Immune Activation and Viral Interference During Sequential Co-Infection with Influenza A Virus and SARS-CoV-2: Molecular Mechanisms, Clinical Evidence, and Therapeutic Implications.International journal of molecular sciences · 2026Review
- DNA oligonucleotides block viral entry of SARS-CoV-2 Omicron variants.PLoS pathogens · 2026Article
- Extra gene coding capacity of SARS-CoV-2 provides a virus engineering platform for in vitro and in vivo applications.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Increased Mannosylation of Extracellular Vesicles in Long COVID Plasma as a Binding Target forInternational journal of molecular sciences · 2026Article
- Dual-Action Niclosamide-Polysaccharide Nasal Spray for the Early Therapeutic Intervention of Respiratory Viral Infections.International journal of molecular sciences · 2026Article
- Secreted ORF8 reprograms macrophages to enhance SARS-CoV-2 infection of lung epithelial cells.bioRxiv : the preprint server for biology · 2026Article
956 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
43 authors at 8 institutions in 3 countries.
Yixuan J HouDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Kenichi OkudaMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Caitlin E EdwardsDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
David R MartinezDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Takanori AsakuraMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Kenneth H DinnonDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Takafumi KatoMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Rhianna E LeeMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Boyd L YountDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Teresa M MascenikMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Gang ChenMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Kenneth N OlivierLaboratory of Chronic Airway Infection, Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Andrew GhioNational Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Chapel Hill, NC, USA.
Longping V TseDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Sarah R LeistDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Lisa E GralinskiDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Alexandra SchäferDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Hong DangMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Rodney GilmoreMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Satoko NakanoMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Ling SunMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
M Leslie FulcherMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Alessandra Livraghi-ButricoMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Nathan I NicelyProtein Expression and Purification Core, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Mark CameronDepartment of Population and Quantitative Health Science, Case Western Reserve University, Cleveland, OH, USA.
Cheryl CameronDepartment of Nutrition, Case Western Reserve University, Cleveland, OH, USA.
David J KelvinDepartment of Microbiology and Immunology, Canadian Center for Vaccinology, Dalhousie University, Halifax, NS, Canada; Laboratory of Immunology, Shantou University Medical College, Shantou, Guangdong, China.
Aravinda de SilvaDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
David M MargolisDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Alena MarkmannDepartment of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Luther BarteltDepartment of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Ross ZumwaltDepartment of Pathology, University of New Mexico, Albuquerque, NM, USA.
Fernando J MartinezDivision of Pulmonary and Critical Care Medicine, Joan & Sanford I. Weill Medical College of Cornell University, New York, NY, USA.
Steven P SalvatoreDepartment of Pathology, Joan & Sanford I. Weill Medical College of Cornell University, New York, NY, USA.
Alain BorczukDepartment of Pathology, Joan & Sanford I. Weill Medical College of Cornell University, New York, NY, USA.
Purushothama R TataDepartment of Cell Biology, Regeneration Next Initiative, Duke University Medical Center, Durham, NC, USA.
Vishwaraj SontakeDepartment of Cell Biology, Regeneration Next Initiative, Duke University Medical Center, Durham, NC, USA.
Adam KimpleDepartment of Otolaryngology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Ilona JaspersDepartment of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Wanda K O'NealMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Scott H RandellMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Richard C BoucherMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: richard_boucher@med.unc.edu.
Ralph S BaricDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: rbaric@email.unc.edu.
University of North Carolina at Chapel Hill · USCornell University · USCase Western Reserve University · USDuke Medical Center · USDalhousie University · CAEnvironmental Protection Agency · USNational Institutes of Health · USUniversity of New Mexico · US
Funding
Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI David Darr · 1985 to 2026
$201.5MUnlocking Zika Virus Immune Control and Pathogenesis with the Collaborative CrossU19AI100625 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BARIC, RALPH S, HEISE, MARK T · 2012 to 2021
$36.6MVector CoreP30DK065988 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Martina Gentzsch · 2004 to 2026
$26.5MThe Biophysics of Mucus Hydration and Adhesion/CohesionP01HL108808 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KESIMER, MEHMET · 2012 to 2021
$23.9MUNC Neuroscience Center Research Cores: MicroscopyP30NS045892 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ZYLKA, MARK J. · 2003 to 2022
$11.5MNorth Carolina Translational and Clinical Science Institute (NC TraCS) KL2KL2TR002490 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WEINBERGER, MORRIS · 2018 to 2022
$11.0MPurinergic Control of CFTR-ENaC Interactions in Alveolar EpitheliaP01HL110873 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BOUCHER, RICHARD CHARLES · 2012 to 2016
$10.7MRespiratory Virus Vaccine and Adjuvant Exploration - Equipment SupplementU01AI149644 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BARIC, RALPH S · 2019 to 2023
$6.1MINFECTIOUS DISEASE PATHOGENESIS TRAININGT32AI007151 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JULIANO, JONATHAN J · 1985 to 2024
$5.5MReceptor recognition mechanisms of coronavirusesR01AI089728 · NIAID · UNIVERSITY OF MINNESOTA · PI Fang Li, Timothy Patrick Sheahan · 2010 to 2026
$4.7MSynthesis of Effective and Safe Mucolytics for Pulmonary DiseaseUH3HL123645 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BOUCHER, RICHARD CHARLES · 2016 to 2018
$4.6MMultiscale Biochemical/Biophysical Integration of Pulmonary Mucus TransportR01HL136961 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BOUCHER, RICHARD CHARLES · 2017 to 2020
$3.2MNCATS NIH HHS KL2 TR002490NCI NIH HHS P30 CA016086NHLBI NIH HHS P01 HL108808NHLBI NIH HHS P01 HL110873NHLBI NIH HHS R00 HL127181NHLBI NIH HHS R01 HL136961NHLBI NIH HHS R01 HL146557NHLBI NIH HHS UH3 HL123645NIAID NIH HHS R01 AI089728NIAID NIH HHS T32 AI007151NIAID NIH HHS U01 AI149644NIAID NIH HHS U19 AI100625NIDDK NIH HHS P30 DK065988NINDS NIH HHS P30 NS045892
Abstract
The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. These findings highlight the nasal susceptibility to SARS-CoV-2 with likely subsequent aspiration-mediated virus seeding to the lung in SARS-CoV-2 pathogenesis. These reagents provide a foundation for investigations into virus-host interactions in protective immunity, host susceptibility, and virus pathogenesis.
Indexed as
AgedAngiotensin-Converting Enzyme 2AnimalsAntibodies, MonoclonalAntibodies, NeutralizingBetacoronavirusCell LineCells, CulturedChlorocebus aethiopsCoronavirus InfectionsCOVID-19COVID-19 SerotherapyCystic FibrosisDNA, RecombinantFemaleFurinACE2 protein, humanAngiotensin-Converting Enzyme 2Antibodies, MonoclonalAntibodies, NeutralizingDNA, RecombinantFurinPeptidyl-Dipeptidase ASerine EndopeptidasesTMPRSS2 protein, humanACE2COVID-19infectious clonenasal infectionneutralization assayprimary cellsreporter virusrespiratory tropismreverse geneticsSARS-CoV-2
Identifiers
What OpenQuestion holds
Textmetadata
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 OpenQuestion graph.