Evidence map›Paper›PMID 36324810›Full record

ArticlebioRxiv : the preprint server for biology2022

Modulation of type I interferon responses potently inhibits SARS-CoV-2 replication and inflammation in rhesus macaques.

Timothy N Hoang, Elise G Viox, Amit A Upadhyay, Zachary Strongin, Gregory K Tharp, Maria Pino, Rayhane Nchioua, Maximilian Hirschenberger, Matthew Gagne, Kevin Nguyen and 28 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. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed, 9 citations in OpenAlex.

  1. From skylight cues to magnetic fields: the toolkit of insect long-distance navigation.Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology · 2026
    Review
  2. The mechanisms and roles of selective autophagy in mammals.Nature reviews. Molecular cell biology · 2023
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

38 authors at 8 institutions in 3 countries.

Timothy N HoangDivision of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Elise G VioxDivision of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Amit A UpadhyayDivision of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Zachary StronginDivision of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Gregory K TharpEmory NPRC Genomics Core Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Maria PinoDivision of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Rayhane NchiouaInstitute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
Maximilian HirschenbergerInstitute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
Matthew GagneVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Kevin NguyenDivision of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Justin L HarperDivision of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Shir MarcianoDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, 76100 Israel.
Arun K BoddapatiEmory NPRC Genomics Core Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Kathryn L PellegriniEmory NPRC Genomics Core Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Jennifer Tisoncik-GoDepartment of Immunology, University of Washington School of Medicine, and the Washington National Primate Research Center, Seattle, WA, 98109, USA.
Leanne S WhitmoreDepartment of Immunology, University of Washington School of Medicine, and the Washington National Primate Research Center, Seattle, WA, 98109, USA.
Kirti A KarunakaranDivision of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Melissa RoyDivision of Pathology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Shannon KirejczykDivision of Pathology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Elizabeth H CurranDivision of Pathology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Chelsea WallaceDivision of Animal Resources, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Jennifer S WoodDivision of Animal Resources, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Fawn Connor-StroudDivision of Animal Resources, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Sudhir P KasturiDivision of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Rebecca D LevitDepartment of Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA.
Michael GaleDepartment of Immunology, University of Washington School of Medicine, and the Washington National Primate Research Center, Seattle, WA, 98109, USA.
Thomas H VanderfordDivision of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Guido SilvestriDivision of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Kathleen Busman-SahayVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Jacob D EstesVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Monica VaccariDivision of Immunology, Tulane National Primate Research Center, Covington, LA 70433, USA.
Daniel C DouekVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Konstantin M J SparrerInstitute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
Frank KirchhoffInstitute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
R Paul JohnsonDivision of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Gideon SchreiberDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, 76100 Israel.
Steven E BosingerDivision of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Mirko PaiardiniDivision of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Emory University · USUniversität Ulm · DEUniversity of Washington · USNational Institutes of Health · USWeizmann Institute of Science · ILOregon Health & Science University · USOregon National Primate Research Center · USTulane University · US

Funding

Washington National Primate Research CenterP51OD010425 · OD · UNIVERSITY OF WASHINGTON · PI Mari Ostendorf · 2012 to 2026
$201.8M
Yerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesisP51OD011132 · OD · EMORY UNIVERSITY · PI Joon Sup Lee · 2012 to 2026
$167.0M
Very early drivers of neutrophilic inflammation in cardiac ischemia-reperfusionR01HL140223 · NHLBI · EMORY UNIVERSITY · PI Rebecca Diane Levit · 2018 to 2026
$4.4M
Illumina NovaSeq 6000 High Throughput DNA Sequencer for Emory UniversityS10OD026799 · OD · EMORY UNIVERSITY · PI BOSINGER, STEVEN EDWARD · 2019 to 2019
$985k
NHLBI NIH HHS R01 HL140223NIH HHS P51 OD010425NIH HHS P51 OD011132NIH HHS S10 OD026799
6 · The paper itself

Abstract

Type-I interferons (IFN-I) are critical mediators of innate control of viral infections, but also drive recruitment of inflammatory cells to sites of infection, a key feature of severe COVID-19. Here, and for the first time, IFN-I signaling was modulated in rhesus macaques (RMs) prior to and during acute SARS-CoV-2 infection using a mutated IFNα2 (IFN-modulator; IFNmod), which has previously been shown to reduce the binding and signaling of endogenous IFN-I. In SARS-CoV-2-infected RMs, IFNmod reduced both antiviral and inflammatory ISGs. Notably, IFNmod treatment resulted in a potent reduction in (i) SARS-CoV-2 viral load in Bronchoalveolar lavage (BAL), upper airways, lung, and hilar lymph nodes; (ii) inflammatory cytokines, chemokines, and CD163+MRC1-inflammatory macrophages in BAL; and (iii) expression of Siglec-1, which enhances SARS-CoV-2 infection and predicts disease severity, on circulating monocytes. In the lung, IFNmod also reduced pathogenesis and attenuated pathways of inflammasome activation and stress response during acute SARS-CoV-2 infection. This study, using an intervention targeting both IFN-α and IFN-β pathways, shows that excessive inflammation driven by type 1 IFN critically contributes to SARS-CoV-2 pathogenesis in RMs, and demonstrates the potential of IFNmod to limit viral replication, SARS-CoV-2 induced inflammation, and COVID-19 severity.

Identifiers

PMID36324810
PMCPMC9628196
OpenAlexW4307280482

What OpenQuestion holds

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Registered trials

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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.