Evidence map›Paper›PMID 28396572›Full record

ArticleEMBO reports2017

Vesicular stomatitis virus N protein-specific single-domain antibody fragments inhibit replication.

Leo Hanke, Florian I Schmidt, Kevin E Knockenhauer, Benjamin Morin, Sean Pj Whelan, Thomas U Schwartz, Hidde L Ploegh

Abstract read
In one paragraph

Article in EMBO reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
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

15 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Exploring cellular biochemistry with nanobodies.The Journal of biological chemistry · 2020
    Review
  9. Applying Antibodies Inside Cells: Principles and Recent Advances in Neurobiology, Virology and Oncology.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2020
    Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. 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.

Leo HankeWhitehead Institute for Biomedical Research, Cambridge, MA, USA.
Florian I SchmidtWhitehead Institute for Biomedical Research, Cambridge, MA, USA.ORCID 0000-0002-9979-9769
Kevin E KnockenhauerDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Benjamin MorinDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
Sean Pj WhelanDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
Thomas U SchwartzDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Hidde L PloeghWhitehead Institute for Biomedical Research, Cambridge, MA, USA hidde.ploegh@childrens.harvard.edu.ORCID 0000-0002-1090-6071

Funding

Overall EvaluationP41GM103403 · NIGMS · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2012 to 2017
$14.3M
RNA Processing in Non-Segmented Minus-Strand RNA VirusesR37AI059371 · NIAID · WASHINGTON UNIVERSITY · PI WHELAN, SEAN PJ · 2015 to 2024
$5.4M
A new strategy to disrupt protein-protein interactions in eukaryotic cells.DP1GM106409 · NIGMS · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI PLOEGH, HIDDE L. · 2012 to 2016
$4.8M
Sortase-mediated protein engineering for the study of host-pathogen interactionsR01AI087879 · NIAID · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI PLOEGH, HIDDE L. · 2010 to 2019
$4.5M
Pixel Array Detector for X-ray CrystallographyS10RR029205 · NCRR · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2010 to 2010
$1.8M
NCRR NIH HHS S10 RR029205NIAID NIH HHS R01 AI087879NIAID NIH HHS R37 AI059371NIGMS NIH HHS DP1 GM106409NIGMS NIH HHS P41 GM103403
6 · The paper itself

Abstract

The transcription and replication machinery of negative-stranded RNA viruses presents a possible target for interference in the viral life cycle. We demonstrate the validity of this concept through the use of cytosolically expressed single-domain antibody fragments (VHHs) that protect cells from a lytic infection with vesicular stomatitis virus (VSV) by targeting the viral nucleoprotein N. We define the binding sites for two such VHHs, 1004 and 1307, by X-ray crystallography to better understand their inhibitory properties. We found that VHH 1307 competes with the polymerase cofactor P for binding and thus inhibits replication and mRNA transcription, while binding of VHH 1004 likely only affects genome replication. The functional relevance of these epitopes is confirmed by the isolation of escape mutants able to replicate in the presence of the inhibitory VHHs. The escape mutations allow identification of the binding site of a third VHH that presumably competes with P for binding at another site than 1307. Collectively, these binding sites uncover different features on the N protein surface that may be suitable for antiviral intervention.

Indexed as

Virus ReplicationA549 CellsAnimalsAntibodies, ViralBinding SitesCrystallography, X-RayDNA ReplicationHumansMutationNucleocapsid ProteinsRNA, ViralSingle-Domain AntibodiesTranscription, GeneticVesicular stomatitis Indiana virusAntibodies, ViralNucleocapsid ProteinsRNA, ViralSingle-Domain Antibodiesantiviralnanobodynegative‐strand RNA virusesvesicular stomatitis virusVHH

Identifiers

PMID28396572
PMCPMC5452021

What OpenQuestion holds

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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.