Evidence map›Paper›PMID 42627087›Full record

ArticleGenetics2026

Systems genetics analysis reveals immune mediators of coronavirus disease severity in mice.

Ellen L Risemberg, Sarah R Leist, Alexandra Schäfer, Kalika D Kamat, Timothy A Bell, Pablo Hock, Kara L Jensen, Colton L Linnertz, Darla R Miller, Ginger D Shaw and 4 more

Abstract read
In one paragraph

Article in Genetics, 2026. 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.

No citing paper in PubMed yet.

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

14 authors.

Ellen L RisembergDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27517, United States.ORCID 0000-0001-6335-1519
Sarah R LeistDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27517, United States.
Alexandra SchäferDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27517, United States.
Kalika D KamatDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27517, United States.
Timothy A BellDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27517, United States.
Pablo HockDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27517, United States.
Kara L JensenDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27517, United States.
Colton L LinnertzDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27517, United States.
Darla R MillerDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27517, United States.
Ginger D ShawDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27517, United States.
Fernando Pardo Manuel de VillenaDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27517, United States.
Ralph S BaricDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27517, United States.
Martin T FerrisDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27517, United States.ORCID 0000-0003-1241-6268
William ValdarDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27517, United States.ORCID 0000-0002-2419-0430

Funding

Unlocking Zika Virus Immune Control and Pathogenesis with the Collaborative CrossU19AI100625 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HEISE, MARK T · 2012 to 2021
$36.6M
Systems Genetics of TuberculosisP01AI181898 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI CHRISTOPHER M SASSETTI · 2024 to 2026
$10.5M
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
Statistical Modeling of Multiparental and Genetic Reference PopulationsR35GM127000 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI William Valdar · 2018 to 2026
$3.1M
Predoctoral Training Program in Bioinformatics and Computational BiologyT32GM135123 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Michael Isaiah Love, William Valdar · 2021 to 2026
$1.7M
NIAID NIH HHS P01 AI181898NIAID NIH HHS R01 AI157253NIAID NIH HHS U19 AI100625NIGMS NIH HHS R35 GM127000NIGMS NIH HHS T32 GM135123NIH HHS P01 AI181898NIH HHS R01 AI157253NIH HHS R35 GM127000NIH HHS T32 GM135123NIH HHS U19 AI100625
6 · The paper itself

Abstract

Severe disease following infection with SARS-CoV or SARS-CoV-2 is driven in part by genetically regulated immune responses that promote lung injury. To study genetic mechanisms of immune-mediated coronavirus pathogenesis, we screened the Collaborative Cross (CC) panel for Mus musculus strains that are phenotypically divergent with respect to coronavirus susceptibility. We identified CC006/TauUnc and CC044/UncJ as susceptible and resistant, respectively, and crossed them in an intercross to produce a genetic mapping population. Previously, we mapped genetic loci associated with disease severity, including HrS43, which is both conserved across viruses and between mouse and human. Here, we incorporate immune cell data from flow cytometry and perform a systems genetics analysis to resolve immune pathways linking host genetic loci to disease outcomes. We identify: (1) immune predictors of disease severity, as revealed by Bayesian variable selection; (2) extensive genetic regulation of the immune system at homeostasis and in response to infection, as revealed by infection-stratified and combined genotype-by-treatment (GxT) QTL mapping; and (3) candidate causal pathways linking genetic loci, immune responses, and disease severity, as revealed by context-dependent Bayesian mediation analysis. Our analysis reveals distinct patterns of virus specificity across biological layers: immune effects on disease severity appear largely consistent across viruses; genetic architecture is both shared and virus-specific; and mediating immune traits are in most cases virus-dependent. Notably, HrS43 appears to influence disease severity through distinct immune mediators in SARS-CoV versus SARS-CoV-2, demonstrating that conserved genetic susceptibility can drive virus-specific immunopathology with translational relevance across species.

Indexed as

Coronavirus InfectionsAnimalsBayes TheoremChromosome MappingCollaborative Cross MiceCOVID-19Genetic Predisposition to DiseaseHumansMiceQuantitative Trait LociSARS-CoV-2Severe acute respiratory syndrome-related coronavirusSeverity of Illness IndexBayesian statisticscollaborative crosscoronavirusgenotype-by-treamentGxTimmune systemimmunologymediation analysismissing data imputationQTL mappingSARS-CoVSARS-CoV-2variable selection

Identifiers

PMID42627087
PMCPMC13643782

What Socratic 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 Socratic graph.