Evidence map›Paper›PMID 34011547›Full record

ArticleJournal of virology2021

Unique Mutations in the Murine Hepatitis Virus Macrodomain Differentially Attenuate Virus Replication, Indicating Multiple Roles for the Macrodomain in Coronavirus Replication.

Lynden S Voth, Joseph J O'Connor, Catherine M Kerr, Ethan Doerger, Nancy Schwarting, Parker Sperstad, David K Johnson, Anthony R Fehr

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 11% 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

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. An autoimmunity-associated allele ofProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Article
  7. Article
  8. An Autoimmunity-associated allele ofbioRxiv : the preprint server for biology · 2025
    Article
  9. Article
  10. The Mac1 ADP-ribosylhydrolase is a Therapeutic Target for SARS-CoV-2.bioRxiv : the preprint server for biology · 2025
    Article
  11. Article
  12. Article
  13. Biomolecular NMR assignments · 2025
    Article
  14. Article
  15. Article
  16. Review
  17. IFN-bioRxiv : the preprint server for biology · 2025
    Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Lynden S Voth *Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, USA.
Joseph J O'Connor *Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, USA.
Catherine M KerrDepartment of Molecular Biosciences, University of Kansas, Lawrence, Kansas, USA.
Ethan DoergerDepartment of Molecular Biosciences, University of Kansas, Lawrence, Kansas, USA.
Nancy SchwartingDepartment of Molecular Biosciences, University of Kansas, Lawrence, Kansas, USA.
Parker SperstadDepartment of Molecular Biosciences, University of Kansas, Lawrence, Kansas, USA.
David K JohnsonMolecular Graphics and Modeling Laboratory and the Computational Chemical Biology Core, University of Kansas, Lawrence, Kansas, USA.
Anthony R FehrDepartment of Molecular Biosciences, University of Kansas, Lawrence, Kansas, USA.
University of Kansas · US

Funding

Synthetic Chemical Biology CoreP20GM113117 · NIGMS · UNIVERSITY OF KANSAS LAWRENCE · PI PERERA, CHAMANI · 2016 to 2025
$23.9M
Graduate Training at the Biology-Chemistry InterfaceT32GM132061 · NIGMS · UNIVERSITY OF KANSAS LAWRENCE · PI Brian Douglas Ackley · 2020 to 2026
$2.9M
Determining mechanisms of innate immune modulation by ADP-ribosylationR35GM138029 · NIGMS · UNIVERSITY OF KANSAS LAWRENCE · PI Anthony R Fehr · 2020 to 2026
$2.7M
Investigating How ADP-ribosylation Impacts Innate Immunity During Coronavirus InfectionK22AI134993 · NIAID · UNIVERSITY OF KANSAS LAWRENCE · PI FEHR, ANTHONY R · 2019 to 2020
$270k
HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) K22AI134993HHS | NIH | National Institute of General Medical Sciences (NIGMS) P20GM113117HHS | NIH | National Institute of General Medical Sciences (NIGMS) R35GM138029HHS | NIH | National Institute of General Medical Sciences (NIGMS) T32GM132061NIAID NIH HHS K22 AI134993NIGMS NIH HHS P20 GM113117NIGMS NIH HHS R35 GM138029NIGMS NIH HHS T32 GM132061University of Kansas (KU) Start-up funds
6 · The paper itself

Abstract

All coronaviruses (CoVs) contain a macrodomain, also termed Mac1, in nonstructural protein 3 (nsp3) that binds and hydrolyzes mono-ADP-ribose (MAR) covalently attached to proteins. Despite several reports demonstrating that Mac1 is a prominent virulence factor, there is still a limited understanding of its cellular roles during infection. Currently, most of the information regarding the role of CoV Mac1 during infection is based on a single point mutation of a highly conserved asparagine residue, which makes contact with the distal ribose of ADP-ribose. To determine if additional Mac1 activities contribute to CoV replication, we compared the replication of murine hepatitis virus (MHV) Mac1 mutants, D1329A and N1465A, to the previously mentioned asparagine mutant, N1347A. These residues contact the adenine and proximal ribose in ADP-ribose, respectively. N1465A had no effect on MHV replication or pathogenesis, while D1329A and N1347A both replicated poorly in bone marrow-derived macrophages (BMDMs), were inhibited by PARP enzymes, and were highly attenuated

Indexed as

Mutation, MissenseViral Nonstructural ProteinsAmino Acid SubstitutionAnimalsHeLa CellsHumansMacrophagesMiceMurine hepatitis virusVirus ReplicationViral Nonstructural ProteinsADP-riboseADP-ribosylationcoronavirusinterferonmacrodomainMHVmouse hepatitis virusNADPARPSARS-CoV-2

Identifiers

PMID34011547
PMCPMC8274620
OpenAlexW3160953642

What OpenQuestion 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 OpenQuestion graph.