Evidence map›Paper›PMID 31095648›Full record

ArticlePLoS pathogens2019

The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression.

Matthew E Grunewald, Yating Chen, Chad Kuny, Takashi Maejima, Robert Lease, Dana Ferraris, Masanori Aikawa, Christopher S Sullivan, Stanley Perlman, Anthony R Fehr

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
151citing papers in PubMed, 1 pooled it
12.2field-weighted citation impact, top 1% 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

151 citing papers in PubMed, 1 synthesis or guideline pooled it, 213 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Review
  6. NADThe Journal of general virology · 2026
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  7. NADFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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  10. Investigation of an association betweenJournal of veterinary research · 2025
    Article
  11. Article
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  14. Article
  15. Article
  16. The Mac1 ADP-ribosylhydrolase is a Therapeutic Target for SARS-CoV-2.bioRxiv : the preprint server for biology · 2025
    Article
  17. Article
  18. Article
  19. Review
  20. Article

91 more citing papers are in PubMed but not listed here.

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

10 authors at 4 institutions in 1 country.

Matthew E GrunewaldDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA, United States of America.
Yating ChenDepartment of Molecular Biosciences, University of Texas, Austin, TX, United States of America.
Chad KunyDepartment of Molecular Biosciences, University of Texas, Austin, TX, United States of America.ORCID 0000-0002-6199-6273
Takashi MaejimaCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America.
Robert LeaseMcDaniel College, Westminster, MD, United States of America.
Dana FerrarisMcDaniel College, Westminster, MD, United States of America.
Masanori AikawaCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America.
Christopher S SullivanDepartment of Molecular Biosciences, University of Texas, Austin, TX, United States of America.
Stanley PerlmanDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA, United States of America.ORCID 0000-0003-4213-2354
Anthony R FehrDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA, United States of America.ORCID 0000-0003-1560-1573
The University of Texas at Austin · USUniversity of Iowa · USBrigham and Women's Hospital · USMcDaniel College · US

Funding

Synthetic Chemical Biology CoreP20GM113117 · NIGMS · UNIVERSITY OF KANSAS LAWRENCE · PI OROZCO, ROBIN C. · 2016 to 2025
$23.9M
SARS-CoV Proteins in Heterologous Viral InfectionP01AI060699 · NIAID · UNIVERSITY OF IOWA · PI GALLAGHER, THOMAS MILLER · 2004 to 2021
$21.5M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007337 · NIGMS · UNIVERSITY OF IOWA · PI GEYER, PAMELA K., LENTZ, STEVEN R · 1985 to 2020
$15.9M
Role of microglia in MHV-induced demyelinationR01NS036592 · NINDS · UNIVERSITY OF IOWA · PI PERLMAN, STANLEY · 1997 to 2021
$6.0M
Role of eicosanoids in pathogenic human CoV infectionsR01AI129269 · NIAID · UNIVERSITY OF IOWA · PI Stanley Perlman · 2016 to 2026
$4.7M
PARP9 and PARP14 in atherosclerosisR01HL126901 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI AIKAWA, MASANORI · 2016 to 2019
$2.4M
Non-coding RNA and ADP-ribosylation in Antiviral DefenseR01AI123231 · NIAID · UNIVERSITY OF TEXAS AT AUSTIN · PI SULLIVAN, CHRISTOPHER S. · 2017 to 2021
$1.9M
Role of anti-SARS-CoV T cell response in pathogenesisR01AI091322 · NIAID · UNIVERSITY OF IOWA · PI PERLMAN, STANLEY · 2011 to 2015
$1.9M
Investigating How ADP-ribosylation Impacts Innate Immunity During Coronavirus InfectionK22AI134993 · NIAID · UNIVERSITY OF KANSAS LAWRENCE · PI FEHR, ANTHONY R · 2019 to 2020
$270k
Deciphering the Role of the Coronavirus Macro Domain in SARS-CoV InfectionF32AI113973 · NIAID · UNIVERSITY OF IOWA · PI FEHR, ANTHONY R · 2014 to 2014
$53k
NHLBI NIH HHS R01 HL126901NIAID NIH HHS F32 AI113973NIAID NIH HHS K22 AI134993NIAID NIH HHS P01 AI060699NIAID NIH HHS R01 AI091322NIAID NIH HHS R01 AI123231NIAID NIH HHS R01 AI129269NIGMS NIH HHS P20 GM113117NIGMS NIH HHS T32 GM007337NINDS NIH HHS R01 NS036592
6 · The paper itself

Abstract

ADP-ribosylation is a ubiquitous post-translational addition of either monomers or polymers of ADP-ribose to target proteins by ADP-ribosyltransferases, usually by interferon-inducible diphtheria toxin-like enzymes known as PARPs. While several PARPs have known antiviral activities, these activities are mostly independent of ADP-ribosylation. Consequently, less is known about the antiviral effects of ADP-ribosylation. Several viral families, including Coronaviridae, Togaviridae, and Hepeviridae, encode for macrodomain proteins that bind to and hydrolyze ADP-ribose from proteins and are critical for optimal replication and virulence. These results suggest that macrodomains counter cellular ADP-ribosylation, but whether PARPs or, alternatively, other ADP-ribosyltransferases cause this modification is not clear. Here we show that pan-PARP inhibition enhanced replication and inhibited interferon production in primary macrophages infected with macrodomain-mutant but not wild-type coronavirus. Specifically, knockdown of two abundantly expressed PARPs, PARP12 and PARP14, led to increased replication of mutant but did not significantly affect wild-type virus. PARP14 was also important for the induction of interferon in mouse and human cells, indicating a critical role for this PARP in the regulation of innate immunity. In summary, these data demonstrate that the macrodomain is required to prevent PARP-mediated inhibition of coronavirus replication and enhancement of interferon production.

Indexed as

Virus ReplicationADP-RibosylationAnimalsCoronavirusCoronavirus InfectionsHumansImmunity, InnateInterferonsMicePoly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesProtein DomainsReceptor, Interferon alpha-betaVirulenceIfnar1 protein, mouseInterferonsPoly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesReceptor, Interferon alpha-beta

Identifiers

PMID31095648
PMCPMC6521996
OpenAlexW2944980314

What OpenQuestion holds

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LicenceCC BY
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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.