Academic Journal
أعرض في EDS

In-Host HEV Quasispecies Evolution Shows the Limits of Mutagenic Antiviral Treatments

التفاصيل البيبلوغرافية
العنوان: In-Host HEV Quasispecies Evolution Shows the Limits of Mutagenic Antiviral Treatments
المؤلفون: Vico-Romero, Judit, Campos, Carolina, Cortese, Maria Francesca, Colomer-Castell, Sergi, Gregori Font, Josep, Garcia-Cehic, Damir, Riveiro-Barciela, Mar, Rando Segura, Ariadna, Ibañez Lligoña, Marta, ADOMBI, Caroline Mélanie, Tabernero, David, Esteban Mur, Juan Ignacio, RODRIGUEZ-FRIAS, FRANCISCO, QUER, JOSEP, Buti Ferret, Maria
المساهمون: Institut Català de la Salut, Colomer-Castell S, Campos C, Quer J Grup de Recerca de les Malalties Hepàtiques, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. Gregori J, Vico-Romero J Grup de Recerca de les Malalties Hepàtiques, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Garcia-Cehic D Grup de Recerca de les Malalties Hepàtiques, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Riveiro-Barciela M, Buti M, Esteban JI Grup de Recerca de les Malalties Hepàtiques, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Rando-Segura A Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Servei de Microbiologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Ibañez-Lligoña M Grup de Recerca de les Malalties Hepàtiques, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Adombi CM Grup de Recerca de les Malalties Hepàtiques, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Institute of Agropastoral Management, University Peleforo Gon Coulibaly, Korhogo, Côte d’Ivoire. Cortese MF, Tabernero D, Rodriguez-Frias F Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Servei de Bioquímica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus
المصدر: Scientia
بيانات النشر: MDPI
سنة النشر: 2023
مصطلحات موضوعية: Medicaments antivírics - Ús terapèutic, Virus de l'hepatitis E - Aspectes genètics, Anomalies cromosòmiques, CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents, ORGANISMS::Viruses::Hepatitis Viruses::Hepatitis E virus, PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Quasispecies, CHEMICALS AND DRUGS::Chemical Actions and Uses::Toxic Actions::Noxae::Mutagens, COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos, ORGANISMOS::virus::virus de hepatitis::virus de la hepatitis E, FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::cuasiespecies, COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones tóxicas::noxas::mutágenos
الوصف: Deep sequencing; Mutagens; Quasispecies ; Seqüenciació profunda; Mutàgens; Quasiespècie ; Secuenciación profunda; Mutágenos; Cuasiespecie ; Here, we report the in-host hepatitis E virus (HEV) quasispecies evolution in a chronically infected patient who was treated with three different regimens of ribavirin (RBV) for nearly 6 years. Sequential plasma samples were collected at different time points and subjected to RNA extraction and deep sequencing using the MiSeq Illumina platforms. Specifically, we RT-PCR amplified a single amplicon from the core region located in the open-reading frame 2 (ORF2). At the nucleotide level (genotype), our analysis showed an increase in the number of rare haplotypes and a drastic reduction in the frequency of the master (most represented) sequence during the period when the virus was found to be insensitive to RBV treatment. Contrarily, at the amino acid level (phenotype), our study revealed conservation of the amino acids, which is represented by a high prevalence of the master sequence. Our findings suggest that using mutagenic antivirals concomitant with high viral loads can lead to the selection and proliferation of a rich set of synonymous haplotypes that express the same phenotype. This can also lead to the selection and proliferation of conservative substitutions that express fitness-enhanced phenotypes. These results have important clinical implications, as they suggest that using mutagenic agents as a monotherapy treatment regimen in the absence of sufficiently effective viral inhibitors can result in diversification and proliferation of a highly diverse quasispecies resistant to further treatment. Therefore, such approaches should be avoided whenever possible. ; This study was partially supported by Plan Estratègic de Recerca i Innovació en Salut (PERIS)—Direcció General de Recerca i Innovació en Salut (DGRIS), Catalan Health Ministry, Generalitat de Catalunya; Centro para el Desarrollo Tecnológico Industrial (CDTI) from the Spanish Ministry of Economy and Business, grant ...
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
تدمد: 1661-6596
Relation: International Journal of Molecular Sciences;24(24); https://doi.org/10.3390/ijms242417185; info:eu-repo/grantAgreement/ES/PEICTI2021-2023/PID2021-126447OB-I00; info:eu-repo/grantAgreement/ES/PE2017-2020/PI19%2F00301; info:eu-repo/grantAgreement/ES/PEICTI2021-2023/PI22%2F00258; Colomer-Castell S, Gregori J, Garcia-Cehic D, Riveiro-Barciela M, Buti M, Rando-Segura A, et al. In-Host HEV Quasispecies Evolution Shows the Limits of Mutagenic Antiviral Treatments. Int J Mol Sci. 2023 Dec 6;24(24):17185.; https://hdl.handle.net/11351/10867; 001130796900001
DOI: 10.3390/ijms242417185
الاتاحة: https://hdl.handle.net/11351/10867
https://doi.org/10.3390/ijms242417185
Rights: Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/openAccess
رقم الانضمام: edsbas.4BFDB4C4
قاعدة البيانات: BASE
الوصف
تدمد:16616596
DOI:10.3390/ijms242417185