Evidence map›Paper›PMID 30281674›Full record

ArticlePloS one2018

Rare haplotype load as marker for lethal mutagenesis.

Josep Gregori, María Eugenia Soria, Isabel Gallego, Mercedes Guerrero-Murillo, Juan Ignacio Esteban, Josep Quer, Celia Perales, Esteban Domingo

Abstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

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  12. Synergistic lethal mutagenesis of hepatitis C virus.Antimicrobial agents and chemotherapy · 2019
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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

8 authors.

Josep GregoriLiver Unit, Liver Disease Laboratory-Viral Hepatitis, Internal Medicine Department, Vall d'Hebron Institut Recerca (VHIR)-Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain.ORCID 0000-0002-4253-8015
María Eugenia SoriaLiver Unit, Liver Disease Laboratory-Viral Hepatitis, Internal Medicine Department, Vall d'Hebron Institut Recerca (VHIR)-Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain.ORCID 0000-0002-4719-3351
Isabel GallegoCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain.
Mercedes Guerrero-MurilloLiver Unit, Liver Disease Laboratory-Viral Hepatitis, Internal Medicine Department, Vall d'Hebron Institut Recerca (VHIR)-Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain.
Juan Ignacio EstebanLiver Unit, Liver Disease Laboratory-Viral Hepatitis, Internal Medicine Department, Vall d'Hebron Institut Recerca (VHIR)-Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain.
Josep QuerLiver Unit, Liver Disease Laboratory-Viral Hepatitis, Internal Medicine Department, Vall d'Hebron Institut Recerca (VHIR)-Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain.ORCID 0000-0003-0014-084X
Celia PeralesLiver Unit, Liver Disease Laboratory-Viral Hepatitis, Internal Medicine Department, Vall d'Hebron Institut Recerca (VHIR)-Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain.ORCID 0000-0003-1618-1937
Esteban DomingoCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

RNA viruses replicate with a template-copying fidelity, which lies close to an extinction threshold. Increases of mutation rate by nucleotide analogues can drive viruses towards extinction. This transition is the basis of an antiviral strategy termed lethal mutagenesis. We have introduced a new diversity index, the rare haplotype load (RHL), to describe NS5B (polymerase) mutant spectra of hepatitis C virus (HCV) populations passaged in absence or presence of the mutagenic agents favipiravir or ribavirin. The increase in RHL is more prominent in mutant spectra whose expansions were due to nucleotide analogues than to multiple passages in absence of mutagens. Statistical tests for paired mutagenized versus non-mutagenized samples with 14 diversity indices show that RHL provides consistently the highest standardized effect of mutagenic treatment difference for ribavirin and favipiravir. The results indicate that the enrichment of viral quasispecies in very low frequency minority genomes can serve as a robust marker for lethal mutagenesis. The diagnostic value of RHL from deep sequencing data is relevant to experimental studies on enhanced mutagenesis of viruses, and to pharmacological evaluations of inhibitors suspected to have a mutagenic activity.

Indexed as

Synthetic Lethal MutationsAmidesAntiviral AgentsCell LineHaplotypesHepacivirusHumansMutation RateNucleosidesPyrazinesQuasispeciesRibavirinRNA-Dependent RNA PolymeraseSerial PassageViral Nonstructural ProteinsAmidesAntiviral AgentsfavipiravirNS-5 protein, hepatitis C virusNucleosidesPyrazinesRibavirinRNA-Dependent RNA PolymeraseViral Nonstructural Proteins

Identifiers

PMID30281674
PMCPMC6169937

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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.