Characterization of in vitro dengue virus resistance to carrageenan

Autores
Talarico, Laura Beatriz; Damonte, Elsa Beatriz
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The λ-carrageenan (λ-car) is a potent and selective inhibitor of dengue virus (DENV) infection targeted to virus adsorption and internalization, due to the structural similarities with the mammalian cell receptor heparan sulfate. To further characterize the antiviral activity of λ-car, the selection and the phenotypic and genomic features of λ-car resistant DENV-2 variants are studied here in comparison to control virus. Resistant variants were rapidly selected in Vero cells after three passages in presence of the drug. No difference was detected in the growth profiles in Vero and C6/36 cells between resistant and control viruses. By contrast, the kinetics of adsorption and internalization of resistant variants in Vero cells was significantly diminished whereas entry to C6/36 cells was unaffected. By plaque purification and sequence analysis of the population, two types of resistant clones were found: some clones presented two mutations in E protein, K126E, and F422L; but other equally λ-car resistant clones had no mutations in E. Furthermore, no mutations were found in other viral proteins like prM, C, or NS1. The genomic disparity in E protein was also associated to differences in phenotype stability. The stable genomic resistance here described provides information about determinants in E protein involved in receptor binding and membrane fusion for uncoating.
Fil: Talarico, Laura Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Damonte, Elsa Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Materia
Dengue Virus
Antiviral Resistance
Carrageenans
Virus Entry
Sulfated Polysaccharides
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/46609

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spelling Characterization of in vitro dengue virus resistance to carrageenanTalarico, Laura BeatrizDamonte, Elsa BeatrizDengue VirusAntiviral ResistanceCarrageenansVirus EntrySulfated Polysaccharideshttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3The λ-carrageenan (λ-car) is a potent and selective inhibitor of dengue virus (DENV) infection targeted to virus adsorption and internalization, due to the structural similarities with the mammalian cell receptor heparan sulfate. To further characterize the antiviral activity of λ-car, the selection and the phenotypic and genomic features of λ-car resistant DENV-2 variants are studied here in comparison to control virus. Resistant variants were rapidly selected in Vero cells after three passages in presence of the drug. No difference was detected in the growth profiles in Vero and C6/36 cells between resistant and control viruses. By contrast, the kinetics of adsorption and internalization of resistant variants in Vero cells was significantly diminished whereas entry to C6/36 cells was unaffected. By plaque purification and sequence analysis of the population, two types of resistant clones were found: some clones presented two mutations in E protein, K126E, and F422L; but other equally λ-car resistant clones had no mutations in E. Furthermore, no mutations were found in other viral proteins like prM, C, or NS1. The genomic disparity in E protein was also associated to differences in phenotype stability. The stable genomic resistance here described provides information about determinants in E protein involved in receptor binding and membrane fusion for uncoating.Fil: Talarico, Laura Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; ArgentinaFil: Damonte, Elsa Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; ArgentinaWiley-liss, Div John Wiley & Sons Inc2016-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/46609Talarico, Laura Beatriz; Damonte, Elsa Beatriz; Characterization of in vitro dengue virus resistance to carrageenan; Wiley-liss, Div John Wiley & Sons Inc; Journal of Medical Virology; 88; 7; 7-2016; 1120-11290146-66151096-9071CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.24457info:eu-repo/semantics/altIdentifier/doi/10.1002/jmv.24457info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:36:32Zoai:ri.conicet.gov.ar:11336/46609instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:36:32.421CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Characterization of in vitro dengue virus resistance to carrageenan
title Characterization of in vitro dengue virus resistance to carrageenan
spellingShingle Characterization of in vitro dengue virus resistance to carrageenan
Talarico, Laura Beatriz
Dengue Virus
Antiviral Resistance
Carrageenans
Virus Entry
Sulfated Polysaccharides
title_short Characterization of in vitro dengue virus resistance to carrageenan
title_full Characterization of in vitro dengue virus resistance to carrageenan
title_fullStr Characterization of in vitro dengue virus resistance to carrageenan
title_full_unstemmed Characterization of in vitro dengue virus resistance to carrageenan
title_sort Characterization of in vitro dengue virus resistance to carrageenan
dc.creator.none.fl_str_mv Talarico, Laura Beatriz
Damonte, Elsa Beatriz
author Talarico, Laura Beatriz
author_facet Talarico, Laura Beatriz
Damonte, Elsa Beatriz
author_role author
author2 Damonte, Elsa Beatriz
author2_role author
dc.subject.none.fl_str_mv Dengue Virus
Antiviral Resistance
Carrageenans
Virus Entry
Sulfated Polysaccharides
topic Dengue Virus
Antiviral Resistance
Carrageenans
Virus Entry
Sulfated Polysaccharides
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The λ-carrageenan (λ-car) is a potent and selective inhibitor of dengue virus (DENV) infection targeted to virus adsorption and internalization, due to the structural similarities with the mammalian cell receptor heparan sulfate. To further characterize the antiviral activity of λ-car, the selection and the phenotypic and genomic features of λ-car resistant DENV-2 variants are studied here in comparison to control virus. Resistant variants were rapidly selected in Vero cells after three passages in presence of the drug. No difference was detected in the growth profiles in Vero and C6/36 cells between resistant and control viruses. By contrast, the kinetics of adsorption and internalization of resistant variants in Vero cells was significantly diminished whereas entry to C6/36 cells was unaffected. By plaque purification and sequence analysis of the population, two types of resistant clones were found: some clones presented two mutations in E protein, K126E, and F422L; but other equally λ-car resistant clones had no mutations in E. Furthermore, no mutations were found in other viral proteins like prM, C, or NS1. The genomic disparity in E protein was also associated to differences in phenotype stability. The stable genomic resistance here described provides information about determinants in E protein involved in receptor binding and membrane fusion for uncoating.
Fil: Talarico, Laura Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Damonte, Elsa Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
description The λ-carrageenan (λ-car) is a potent and selective inhibitor of dengue virus (DENV) infection targeted to virus adsorption and internalization, due to the structural similarities with the mammalian cell receptor heparan sulfate. To further characterize the antiviral activity of λ-car, the selection and the phenotypic and genomic features of λ-car resistant DENV-2 variants are studied here in comparison to control virus. Resistant variants were rapidly selected in Vero cells after three passages in presence of the drug. No difference was detected in the growth profiles in Vero and C6/36 cells between resistant and control viruses. By contrast, the kinetics of adsorption and internalization of resistant variants in Vero cells was significantly diminished whereas entry to C6/36 cells was unaffected. By plaque purification and sequence analysis of the population, two types of resistant clones were found: some clones presented two mutations in E protein, K126E, and F422L; but other equally λ-car resistant clones had no mutations in E. Furthermore, no mutations were found in other viral proteins like prM, C, or NS1. The genomic disparity in E protein was also associated to differences in phenotype stability. The stable genomic resistance here described provides information about determinants in E protein involved in receptor binding and membrane fusion for uncoating.
publishDate 2016
dc.date.none.fl_str_mv 2016-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/46609
Talarico, Laura Beatriz; Damonte, Elsa Beatriz; Characterization of in vitro dengue virus resistance to carrageenan; Wiley-liss, Div John Wiley & Sons Inc; Journal of Medical Virology; 88; 7; 7-2016; 1120-1129
0146-6615
1096-9071
CONICET Digital
CONICET
url http://hdl.handle.net/11336/46609
identifier_str_mv Talarico, Laura Beatriz; Damonte, Elsa Beatriz; Characterization of in vitro dengue virus resistance to carrageenan; Wiley-liss, Div John Wiley & Sons Inc; Journal of Medical Virology; 88; 7; 7-2016; 1120-1129
0146-6615
1096-9071
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.24457
info:eu-repo/semantics/altIdentifier/doi/10.1002/jmv.24457
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley-liss, Div John Wiley & Sons Inc
publisher.none.fl_str_mv Wiley-liss, Div John Wiley & Sons Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
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repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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