Evidence map›Paper›PMID 33067384›Full record

ArticlemBio2020

SARS-CoV-2 Is Restricted by Zinc Finger Antiviral Protein despite Preadaptation to the Low-CpG Environment in Humans.

Rayhane Nchioua, Dorota Kmiec, Janis A Müller, Carina Conzelmann, Rüdiger Groß, Chad M Swanson, Stuart J D Neil, Steffen Stenger, Daniel Sauter, Jan Münch and 2 more

Open access · goldAbstract read
In one paragraph

Article in mBio, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed
9.9field-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

96 citing papers in PubMed, 154 citations in OpenAlex.

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  19. A Genetic Circuit Design for Targeted Viral RNA Degradation.Bioengineering (Basel, Switzerland) · 2023
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36 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

12 authors at 3 institutions in 2 countries.

Rayhane NchiouaInstitute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
Dorota KmiecInstitute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
Janis A MüllerInstitute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
Carina ConzelmannInstitute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
Rüdiger GroßInstitute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
Chad M SwansonDepartment of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom.ORCID 0000-0002-6650-3634
Stuart J D NeilDepartment of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom.
Steffen StengerInstitute of Medical Microbiology and Hygiene, Ulm University Medical Center, Ulm, Germany.
Daniel SauterInstitute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.ORCID 0000-0001-7665-0040
Jan MünchInstitute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
Konstantin M J SparrerInstitute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
Frank KirchhoffInstitute of Molecular Virology, Ulm University Medical Center, Ulm, Germany frank.kirchhoff@uni-ulm.de.ORCID 0000-0002-7052-2360
Universität Ulm · DEKing's College London · GBInstitute of Medical Microbiology and Hygiene · DE

Funding

Medical Research Council MC_PC_14105Medical Research Council MC_PC_15068Medical Research Council MR/S000844/1
6 · The paper itself

Abstract

Recent evidence shows that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sensitive to interferons (IFNs). However, the most effective types of IFNs and the underlying antiviral effectors remain to be defined. Here, we show that zinc finger antiviral protein (ZAP), which preferentially targets CpG dinucleotides in viral RNA sequences, restricts SARS-CoV-2. We further demonstrate that ZAP and its cofactors KHNYN and TRIM25 are expressed in human lung cells. Type I, II, and III IFNs all strongly inhibited SARS-CoV-2 and further induced ZAP expression. Comprehensive sequence analyses revealed that SARS-CoV-2 and its closest relatives from horseshoe bats showed the strongest CpG suppression among all known human and bat coronaviruses, respectively. Nevertheless, endogenous ZAP expression restricted SARS-CoV-2 replication in human lung cells, particularly upon treatment with IFN-α or IFN-γ. Both the long and the short isoforms of human ZAP reduced SARS-CoV-2 RNA expression levels, but the former did so with greater efficiency. Finally, we show that the ability to restrict SARS-CoV-2 is conserved in ZAP orthologues of the reservoir bat and potential intermediate pangolin hosts of human coronaviruses. Altogether, our results show that ZAP is an important effector of the innate response against SARS-CoV-2, although this pandemic pathogen emerged from zoonosis of a coronavirus that was preadapted to the low-CpG environment in humans.

Indexed as

CpG IslandsAnimalsBetacoronavirusCell LineCoronavirusCoronavirus InfectionsCOVID-19Gene ExpressionGenome, ViralHumansInterferonsPandemicsPhylogenyPneumonia, ViralProtein IsoformsRNA-Binding ProteinsInterferonsProtein IsoformsRNA-Binding ProteinsRNA, ViralZC3HAV1 protein, humanCOVID-19CpG suppressionevolutioninterferonSARS-CoV-2ZAP

Identifiers

PMID33067384
PMCPMC7569149
OpenAlexW3093413235

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.