Evidence map›Paper›PMID 38257840›Full record

ArticleViruses2024

Retinoic Acid-Mediated Inhibition of Mouse Coronavirus Replication Is Dependent on IRF3 and CaMKK.

Justin H Franco, Ryan A Harris, William G Ryan, Roger Travis Taylor, Robert E McCullumsmith, Saurabh Chattopadhyay, Zhixing K Pan

Open access · goldAbstract read
In one paragraph

Article in Viruses, 2024. 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
0.5field-weighted citation impact, top 39% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Article
  2. 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

7 authors at 2 institutions in 1 country.

Justin H FrancoDepartment of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.ORCID 0000-0001-5503-8928
Ryan A HarrisDepartment of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
William G RyanDepartment of Neurosciences and Neurological Disorders, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.ORCID 0000-0003-4868-4002
Roger Travis TaylorDepartment of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.ORCID 0000-0002-3819-8548
Robert E McCullumsmithDepartment of Neurosciences and Neurological Disorders, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
Saurabh ChattopadhyayDepartment of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.ORCID 0000-0002-2930-1523
Zhixing K PanDepartment of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
University of Toledo · USUniversity of Kentucky · US

Funding

Anti-inflammatory functions for non-transcriptional IRF3R01AI155545 · NIAID · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI Saurabh Chattopadhyay · 2021 to 2026
$2.2M
Understanding the proviral role for TRAF6 interaction with the viral protease in flavivirus replication and pathogenesisR01AI153496 · NIAID · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI TAYLOR, ROGER TRAVIS · 2020 to 2024
$1.9M
Novel antiviral mechanisms of the interferon systemR01AI165521 · NIAID · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI Saurabh Chattopadhyay · 2022 to 2026
$1.7M
Training in Molecular and translational Cell DynamicsT32GM144873 · NIGMS · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI AVIDOR-REISS, TOMER, DWORKIN, LANCE DOUGLAS · 2022 to 2024
$1.3M
NIAID NIH HHS R01 AI153496NIAID NIH HHS R01 AI155545NIAID NIH HHS R01 AI165521NIGMS NIH HHS T32 GM144873
6 · The paper itself

Abstract

The ongoing COVID-19 pandemic has revealed the shortfalls in our understanding of how to treat coronavirus infections. With almost 7 million case fatalities of COVID-19 globally, the catalog of FDA-approved antiviral therapeutics is limited compared to other medications, such as antibiotics. All-trans retinoic acid (RA), or activated vitamin A, has been studied as a potential therapeutic against coronavirus infection because of its antiviral properties. Due to its impact on different signaling pathways, RA's mechanism of action during coronavirus infection has not been thoroughly described. To determine RA's mechanism of action, we examined its effect against a mouse coronavirus, mouse hepatitis virus strain A59 (MHV). We demonstrated that RA significantly decreased viral titers in infected mouse L929 fibroblasts and RAW 264.7 macrophages. The reduced viral titers were associated with a corresponding decrease in MHV nucleocapsid protein expression. Using interferon regulatory factor 3 (IRF3) knockout RAW 264.7 cells, we demonstrated that RA-induced suppression of MHV required IRF3 activity. RNA-seq analysis of wildtype and IRF3 knockout RAW cells showed that RA upregulated calcium/calmodulin (CaM) signaling proteins, such as CaM kinase kinase 1 (CaMKK1). When treated with a CaMKK inhibitor, RA was unable to upregulate IRF activation during MHV infection. In conclusion, our results demonstrate that RA-induced protection against coronavirus infection depends on IRF3 and CaMKK.

Indexed as

Calcium-Calmodulin-Dependent Protein Kinase KinaseInterferon Regulatory Factor-3Murine hepatitis virusTretinoinVirus ReplicationAmino AcidsAnimalsAntiviral AgentsL CellsMiceRAW 264.7 CellsAmino AcidsAntiviral AgentsCalcium-Calmodulin-Dependent Protein Kinase KinaseInterferon Regulatory Factor-3TretinoinCaMKKcoronavirusIRF3MHVretinoic acid

Identifiers

PMID38257840
PMCPMC10819102
OpenAlexW4390976120

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.