Evidence map›Paper›PMID 34062120›Full record

ArticleCell2021

TRIM7 inhibits enterovirus replication and promotes emergence of a viral variant with increased pathogenicity.

Wenchun Fan, Katrina B Mar, Levent Sari, Ilona K Gaszek, Qiang Cheng, Bret M Evers, John M Shelton, Mary Wight-Carter, Daniel J Siegwart, Milo M Lin and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

58 citing papers in PubMed, 81 citations in OpenAlex.

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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

11 authors at 1 institution in 1 country.

Wenchun FanDepartment of Microbiology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Katrina B MarDepartment of Microbiology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Levent SariGreen Center for Molecular, Computational, and Systems Biology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Ilona K GaszekGreen Center for Molecular, Computational, and Systems Biology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Qiang ChengDepartment of Biochemistry, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Bret M EversDepartments of Pathology and Ophthalmology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
John M SheltonDepartment of Internal Medicine, Histo Pathology Core Division, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Mary Wight-CarterAnimal Resource Center, UT Southwestern Medical Center, Dallas, TX, USA.
Daniel J SiegwartDepartment of Biochemistry, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Milo M LinGreen Center for Molecular, Computational, and Systems Biology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
John W SchogginsDepartment of Microbiology, UT Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: john.schoggins@utsouthwestern.edu.
Southwestern Medical Center · US

Funding

INTEGRATIVE IMMUNOLOGY TRAINING PROGRAMT32AI005284 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI Nan Yan · 2003 to 2026
$7.4M
A functional evolutionary genetic approach to combat viral infectionDP1AI158124 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI SCHOGGINS, JOHN W. · 2020 to 2024
$5.7M
Discovery of antiviral mechanisms in batsDP2AI117922 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI SCHOGGINS, JOHN W. · 2014 to 2016
$2.6M
NIAID NIH HHS DP1 AI158124NIAID NIH HHS DP2 AI117922NIAID NIH HHS T32 AI005284
6 · The paper itself

Abstract

To control viral infection, vertebrates rely on both inducible interferon responses and less well-characterized cell-intrinsic responses composed of "at the ready" antiviral effector proteins. Here, we show that E3 ubiquitin ligase TRIM7 is a cell-intrinsic antiviral effector that restricts multiple human enteroviruses by targeting viral 2BC, a membrane remodeling protein, for ubiquitination and proteasome-dependent degradation. Selective pressure exerted by TRIM7 results in emergence of a TRIM7-resistant coxsackievirus with a single point mutation in the viral 2C ATPase/helicase. In cultured cells, the mutation helps the virus evade TRIM7 but impairs optimal viral replication, and this correlates with a hyperactive and structurally plastic 2C ATPase. Unexpectedly, the TRIM7-resistant virus has a replication advantage in mice and causes lethal pancreatitis. These findings reveal a unique mechanism for targeting enterovirus replication and provide molecular insight into the benefits and trade-offs of viral evolution imposed by a host restriction factor.

Indexed as

Adenosine TriphosphatasesAnimalsCell LineEnterovirusFemaleHumansInflammationMiceMice, Inbred C57BLMutationProteasome Endopeptidase ComplexProtein BindingProteolysisRNA, ViralTripartite Motif ProteinsUbiquitinAdenosine TriphosphatasesProteasome Endopeptidase ComplexRNA, ViralTRIM7 protein, humanTrim7 protein, mouseTripartite Motif ProteinsUbiquitinUbiquitin-Protein LigasesViral ProteinsAntiviral immunityE3 ubiquitin ligaseEnterovirusRestriction factorViral evolutionViral pathogenesis

Identifiers

PMID34062120
PMCPMC8276836
OpenAlexW3165732305

What OpenQuestion holds

Textmetadata
LicenceTDM
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.