دورية أكاديمية
أعرض في EDS

Rare haplotype load as marker for lethal mutagenesis.

التفاصيل البيبلوغرافية
العنوان: Rare haplotype load as marker for lethal mutagenesis.
المؤلفون: Gregori J; Liver Unit, Liver Disease Laboratory-Viral Hepatitis, Internal Medicine Department, Vall d'Hebron Institut Recerca (VHIR)-Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain.; Roche Diagnostics, S.L., Sant Cugat del Vallés, Barcelona, Spain., Soria ME; Liver Unit, Liver Disease Laboratory-Viral Hepatitis, Internal Medicine Department, Vall d'Hebron Institut Recerca (VHIR)-Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain., Gallego I; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain.; Centro de Biología Molecular 'Severo Ochoa' (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, Madrid, Spain., Guerrero-Murillo M; Liver Unit, Liver Disease Laboratory-Viral Hepatitis, Internal Medicine Department, Vall d'Hebron Institut Recerca (VHIR)-Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain., Esteban JI; Liver Unit, Liver Disease Laboratory-Viral Hepatitis, Internal Medicine Department, Vall d'Hebron Institut Recerca (VHIR)-Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain.; Universitat Autónoma de Barcelona, Barcelona, Spain., Quer J; Liver Unit, Liver Disease Laboratory-Viral Hepatitis, Internal Medicine Department, Vall d'Hebron Institut Recerca (VHIR)-Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain.; Universitat Autónoma de Barcelona, Barcelona, Spain., Perales C; Liver Unit, Liver Disease Laboratory-Viral Hepatitis, Internal Medicine Department, Vall d'Hebron Institut Recerca (VHIR)-Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain.; Centro de Biología Molecular 'Severo Ochoa' (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, Madrid, Spain., Domingo E; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain.; Centro de Biología Molecular 'Severo Ochoa' (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, Madrid, Spain.
المصدر: PloS one [PLoS One] 2018 Oct 03; Vol. 13 (10), pp. e0204877. Date of Electronic Publication: 2018 Oct 03 (Print Publication: 2018).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Synthetic Lethal Mutations*, Antiviral Agents/*pharmacology , Hepacivirus/*genetics , Viral Nonstructural Proteins/*genetics, Amides/pharmacology ; Cell Line ; Haplotypes ; Humans ; Mutation Rate ; Nucleosides/analogs & derivatives ; Pyrazines/pharmacology ; Quasispecies ; Ribavirin/pharmacology ; Serial Passage
مستخلص: 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.
Competing Interests: The funder “Roche Diagnostics S.L.” provided support in the form of salaries for author [JG], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. No other Competing Interests to declare. Thus, our adherence to PLOS ONE policies on sharing data and materials is not altered.
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المشرفين على المادة: 0 (Amides)
0 (Antiviral Agents)
0 (Nucleosides)
0 (Pyrazines)
0 (Viral Nonstructural Proteins)
49717AWG6K (Ribavirin)
EC 2.7.7.48 (NS-5 protein, hepatitis C virus)
EW5GL2X7E0 (favipiravir)
تواريخ الأحداث: Date Created: 20181004 Date Completed: 20190322 Latest Revision: 20220110
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6169937
DOI: 10.1371/journal.pone.0204877
PMID: 30281674
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0204877