Evidence map›Paper›PMID 38508400›Full record

ArticleVirus research2024

Genetic loci regulate Sarbecovirus pathogenesis: A comparison across mice and humans.

Alexandra Schäfer, Lisa E Gralinski, Sarah R Leist, Brea K Hampton, Michael A Mooney, Kara L Jensen, Rachel L Graham, Sudhakar Agnihothram, Sophia Jeng, Steven Chamberlin and 15 more

Open access · goldAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Virus research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.4field-weighted citation impact, top 14% of its field
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

9 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Article
  3. Mechanisms of sex differences in acute and long COVID sequelae in mice.bioRxiv : the preprint server for biology · 2025
    Article
  4. Review
  5. Article
  6. Article
  7. Animal models of Long Covid: A hit-and-run disease.Science translational medicine · 2024
    Review
  8. Article
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors at 4 institutions in 1 country.

Alexandra SchäferDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: aschaefe@email.unc.edu.
Lisa E GralinskiDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: lgralins@email.unc.edu.
Sarah R LeistDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Brea K HamptonDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Michael A MooneyKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Division of Bioinformatics and Computational Biology, Oregon Health & Science University, Portland, OR, USA; Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA.
Kara L JensenDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Rachel L GrahamDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Sudhakar AgnihothramDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Sophia JengKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, OR, USA.
Steven ChamberlinDivision of Bioinformatics and Computational Biology, Oregon Health & Science University, Portland, OR, USA; Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA.
Timothy A BellDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
D Trevor ScobeyDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Colton L LinnertzDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Laura A VanBlarganDepartment of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Larissa B ThackrayDepartment of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Pablo HockDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Darla R MillerDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Ginger D ShawDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Michael S DiamondDepartment of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology & Immunology2, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology3, Washington University School of Medicine, St. Louis, MO, USA.
Fernando Pardo Manuel de VillenaDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Shannon K McWeeneyKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Division of Bioinformatics and Computational Biology, Oregon Health & Science University, Portland, OR, USA; Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA; Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, OR, USA.
Mark T HeiseDepartment of Genetics, 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; Rapidly Emerging Antiviral Drug Discovery Initiative, University of North Carolina, Chapel Hill NC, USA.
Vineet D MenacheryDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston TX, USA; Department of Pathology and Center for Biodefense & Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX, USA.
Martin T FerrisDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: mtferris@email.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; Rapidly Emerging Antiviral Drug Discovery Initiative, University of North Carolina, Chapel Hill NC, USA. Electronic address: rsbaric@email.unc.edu.
University of North Carolina at Chapel Hill · USWashington University in St. Louis · USOregon Health & Science University · USOregon Clinic · US

Funding

Oregon Clinical and Translational Research Institute - The National COVID Cohort Collaborative (N3C)UL1TR002369 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI Cynthia D Morris, Christopher G. Slatore · 2017 to 2026
$78.4M
Unlocking Zika Virus Immune Control and Pathogenesis with the Collaborative CrossU19AI100625 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BARIC, RALPH S · 2012 to 2021
$36.6M
Translational CoreU19AI109761 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LIPKIN, W. IAN · 2014 to 2018
$32.6M
Structure-based design of broadly protective coronavirus vaccinesP01AI167966 · NIAID · UNIVERSITY OF WASHINGTON · PI Francois J Villinger · 2022 to 2026
$15.3M
Respiratory Virus Vaccine and Adjuvant Exploration - Equipment SupplementU01AI149644 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BARIC, RALPH S · 2019 to 2023
$6.1M
Human antibody-based countermeasures against the Wuhan Coronavirus SARS-CoV-2R01AI157155 · NIAID · WASHINGTON UNIVERSITY · PI BARIC, RALPH S, CROWE, JAMES E · 2020 to 2024
$6.0M
Genetic Analysis of COVID-19 Susceptibility and Resistance Determinants in the Collaborative CrossR01AI157253 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BARIC, RALPH S, HEISE, MARK T · 2020 to 2024
$3.8M
Systems Based Analysis of Host Factors that Contribute to Aging PathogenesisR00AG049092 · NIA · UNIVERSITY OF TEXAS MED BR GALVESTON · PI MENACHERY, VINEET D · 2017 to 2019
$736k
Identifying Genetic Regulators and New Models of Wild Type Coronavirus PathogenesisR21AI145372 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI GRALINSKI, LISA · 2020 to 2021
$389k
Evaluating the role of cytomegalovirus and age on lung immune homeostasis and responses to respiratory infectionsK00AG073570 · NIA · UNIVERSITY OF ARIZONA · PI BROWN, BREA HAMPTON · 2022 to 2024
$228k
NCATS NIH HHS UL1 TR002369NIAID NIH HHS P01 AI167966NIAID NIH HHS R01 AI157155NIAID NIH HHS R01 AI157253NIAID NIH HHS R21 AI145372NIAID NIH HHS U01 AI149644NIAID NIH HHS U19 AI100625NIAID NIH HHS U19 AI109761NIA NIH HHS K00 AG073570NIA NIH HHS R00 AG049092
6 · The paper itself

Abstract

Coronavirus (CoV) cause considerable morbidity and mortality in humans and other mammals, as evidenced by the emergence of Severe Acute Respiratory CoV (SARS-CoV) in 2003, Middle East Respiratory CoV (MERS-CoV) in 2012, and SARS-CoV-2 in 2019. Although poorly characterized, natural genetic variation in human and other mammals modulate virus pathogenesis, as reflected by the spectrum of clinical outcomes ranging from asymptomatic infections to lethal disease. Using multiple human epidemic and zoonotic Sarbecoviruses, coupled with murine Collaborative Cross genetic reference populations, we identify several dozen quantitative trait loci that regulate SARS-like group-2B CoV pathogenesis and replication. Under a Chr4 QTL, we deleted a candidate interferon stimulated gene, Trim14 which resulted in enhanced SARS-CoV titers and clinical disease, suggesting an antiviral role during infection. Importantly, about 60 % of the murine QTL encode susceptibility genes identified as priority candidates from human genome-wide association studies (GWAS) studies after SARS-CoV-2 infection, suggesting that similar selective forces have targeted analogous genes and pathways to regulate Sarbecovirus disease across diverse mammalian hosts. These studies provide an experimental platform in rodents to investigate the molecular-genetic mechanisms by which potential cross mammalian susceptibility loci and genes regulate type-specific and cross-SARS-like group 2B CoV replication, immunity, and pathogenesis in rodent models. Our study also provides a paradigm for identifying susceptibility loci for other highly heterogeneous and virulent viruses that sporadically emerge from zoonotic reservoirs to plague human and animal populations.

Indexed as

Quantitative Trait LociAnimalsCOVID-19Disease Models, AnimalGenome-Wide Association StudyHumansMiceSARS-CoV-2Tripartite Motif ProteinsVirus ReplicationTripartite Motif ProteinsHost susceptibility lociPathogenesisSARS-CoVSARS-CoV-2Zoonotic CoV

Identifiers

PMID38508400
PMCPMC10981091
OpenAlexW4393123385

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.