In vitro isolation of variants of herpes simplex virus attenuated with altered thymidine kinase and DNA polymerase genes using carrageenans as selection agents

Autores
Mateu, Cecilia Gabriela; Artuso, María Carolina; Pujol, Carlos Alberto; Linero, Florencia Natalia; Scolaro, Luis Alberto; Carlucci, Maria Josefina
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Natural polysaccharides known as carrageenans are potent and selective inhibitors of herpes simplex virus through blocking the interaction of the virus with the cellular receptor. Passaging the virus in vitro in the presence of carrageenans types k and ι enabled us to generate variants of herpes simplex type 2. At passage 22, four clones were selected for further characterization: ι22-9, ι22-12, k22-12 and k22-13. Variants showed a syncytial phenotype, grew at similar titers when compared to parental virus and exhibited moderate resistance to carrageenans. These were found to have a mutation in the thymidine kinase gene in the case of k22-13 (aa 149 Val to Ala) and in the DNA pol gene in the case of ι22-12 (aa 789 Met to Thr). In variant k22-12, three substitutions in the DNA pol gene were identified. Variants were less virulent than parental strain when tested intravaginally or intranasally in mice. Attenuation correlated with higher levels of IL-6 and TNF-α in animals inoculated with the variants. Selective pressure on the external glycoproteins of the virus may generate viruses with alterations in genes unrelated to the target of action of the selection agent. Study of this type of variation might help us to understand the basis of persistent viral strategies, which in turn may play a role in the development of virus-host symbioses.
Fil: Mateu, Cecilia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Artuso, María Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Pujol, Carlos Alberto. 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: Linero, Florencia Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Scolaro, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Carlucci, Maria Josefina. 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
Carrageenan
Herpesvirus
Mutants
Pathogenicity
Syncytial Variant
Virulence
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:11336/59594

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network_name_str CONICET Digital (CONICET)
spelling In vitro isolation of variants of herpes simplex virus attenuated with altered thymidine kinase and DNA polymerase genes using carrageenans as selection agentsMateu, Cecilia GabrielaArtuso, María CarolinaPujol, Carlos AlbertoLinero, Florencia NataliaScolaro, Luis AlbertoCarlucci, Maria JosefinaCarrageenanHerpesvirusMutantsPathogenicitySyncytial VariantVirulencehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Natural polysaccharides known as carrageenans are potent and selective inhibitors of herpes simplex virus through blocking the interaction of the virus with the cellular receptor. Passaging the virus in vitro in the presence of carrageenans types k and ι enabled us to generate variants of herpes simplex type 2. At passage 22, four clones were selected for further characterization: ι22-9, ι22-12, k22-12 and k22-13. Variants showed a syncytial phenotype, grew at similar titers when compared to parental virus and exhibited moderate resistance to carrageenans. These were found to have a mutation in the thymidine kinase gene in the case of k22-13 (aa 149 Val to Ala) and in the DNA pol gene in the case of ι22-12 (aa 789 Met to Thr). In variant k22-12, three substitutions in the DNA pol gene were identified. Variants were less virulent than parental strain when tested intravaginally or intranasally in mice. Attenuation correlated with higher levels of IL-6 and TNF-α in animals inoculated with the variants. Selective pressure on the external glycoproteins of the virus may generate viruses with alterations in genes unrelated to the target of action of the selection agent. Study of this type of variation might help us to understand the basis of persistent viral strategies, which in turn may play a role in the development of virus-host symbioses.Fil: Mateu, Cecilia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; ArgentinaFil: Artuso, María Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; ArgentinaFil: Pujol, Carlos Alberto. 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: Linero, Florencia Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; ArgentinaFil: Scolaro, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; ArgentinaFil: Carlucci, Maria Josefina. 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; ArgentinaSpringer2017-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/59594Mateu, Cecilia Gabriela; Artuso, María Carolina; Pujol, Carlos Alberto; Linero, Florencia Natalia; Scolaro, Luis Alberto; et al.; In vitro isolation of variants of herpes simplex virus attenuated with altered thymidine kinase and DNA polymerase genes using carrageenans as selection agents; Springer; Symbiosis; 72; 1; 5-2017; 23-300334-5114CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1007/s13199-016-0437-4info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s13199-016-0437-4info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:29:23Zoai:ri.conicet.gov.ar:11336/59594instacron: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 14:29:24.188CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv In vitro isolation of variants of herpes simplex virus attenuated with altered thymidine kinase and DNA polymerase genes using carrageenans as selection agents
title In vitro isolation of variants of herpes simplex virus attenuated with altered thymidine kinase and DNA polymerase genes using carrageenans as selection agents
spellingShingle In vitro isolation of variants of herpes simplex virus attenuated with altered thymidine kinase and DNA polymerase genes using carrageenans as selection agents
Mateu, Cecilia Gabriela
Carrageenan
Herpesvirus
Mutants
Pathogenicity
Syncytial Variant
Virulence
title_short In vitro isolation of variants of herpes simplex virus attenuated with altered thymidine kinase and DNA polymerase genes using carrageenans as selection agents
title_full In vitro isolation of variants of herpes simplex virus attenuated with altered thymidine kinase and DNA polymerase genes using carrageenans as selection agents
title_fullStr In vitro isolation of variants of herpes simplex virus attenuated with altered thymidine kinase and DNA polymerase genes using carrageenans as selection agents
title_full_unstemmed In vitro isolation of variants of herpes simplex virus attenuated with altered thymidine kinase and DNA polymerase genes using carrageenans as selection agents
title_sort In vitro isolation of variants of herpes simplex virus attenuated with altered thymidine kinase and DNA polymerase genes using carrageenans as selection agents
dc.creator.none.fl_str_mv Mateu, Cecilia Gabriela
Artuso, María Carolina
Pujol, Carlos Alberto
Linero, Florencia Natalia
Scolaro, Luis Alberto
Carlucci, Maria Josefina
author Mateu, Cecilia Gabriela
author_facet Mateu, Cecilia Gabriela
Artuso, María Carolina
Pujol, Carlos Alberto
Linero, Florencia Natalia
Scolaro, Luis Alberto
Carlucci, Maria Josefina
author_role author
author2 Artuso, María Carolina
Pujol, Carlos Alberto
Linero, Florencia Natalia
Scolaro, Luis Alberto
Carlucci, Maria Josefina
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Carrageenan
Herpesvirus
Mutants
Pathogenicity
Syncytial Variant
Virulence
topic Carrageenan
Herpesvirus
Mutants
Pathogenicity
Syncytial Variant
Virulence
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Natural polysaccharides known as carrageenans are potent and selective inhibitors of herpes simplex virus through blocking the interaction of the virus with the cellular receptor. Passaging the virus in vitro in the presence of carrageenans types k and ι enabled us to generate variants of herpes simplex type 2. At passage 22, four clones were selected for further characterization: ι22-9, ι22-12, k22-12 and k22-13. Variants showed a syncytial phenotype, grew at similar titers when compared to parental virus and exhibited moderate resistance to carrageenans. These were found to have a mutation in the thymidine kinase gene in the case of k22-13 (aa 149 Val to Ala) and in the DNA pol gene in the case of ι22-12 (aa 789 Met to Thr). In variant k22-12, three substitutions in the DNA pol gene were identified. Variants were less virulent than parental strain when tested intravaginally or intranasally in mice. Attenuation correlated with higher levels of IL-6 and TNF-α in animals inoculated with the variants. Selective pressure on the external glycoproteins of the virus may generate viruses with alterations in genes unrelated to the target of action of the selection agent. Study of this type of variation might help us to understand the basis of persistent viral strategies, which in turn may play a role in the development of virus-host symbioses.
Fil: Mateu, Cecilia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Artuso, María Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Pujol, Carlos Alberto. 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: Linero, Florencia Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Scolaro, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Carlucci, Maria Josefina. 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 Natural polysaccharides known as carrageenans are potent and selective inhibitors of herpes simplex virus through blocking the interaction of the virus with the cellular receptor. Passaging the virus in vitro in the presence of carrageenans types k and ι enabled us to generate variants of herpes simplex type 2. At passage 22, four clones were selected for further characterization: ι22-9, ι22-12, k22-12 and k22-13. Variants showed a syncytial phenotype, grew at similar titers when compared to parental virus and exhibited moderate resistance to carrageenans. These were found to have a mutation in the thymidine kinase gene in the case of k22-13 (aa 149 Val to Ala) and in the DNA pol gene in the case of ι22-12 (aa 789 Met to Thr). In variant k22-12, three substitutions in the DNA pol gene were identified. Variants were less virulent than parental strain when tested intravaginally or intranasally in mice. Attenuation correlated with higher levels of IL-6 and TNF-α in animals inoculated with the variants. Selective pressure on the external glycoproteins of the virus may generate viruses with alterations in genes unrelated to the target of action of the selection agent. Study of this type of variation might help us to understand the basis of persistent viral strategies, which in turn may play a role in the development of virus-host symbioses.
publishDate 2017
dc.date.none.fl_str_mv 2017-05
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/11336/59594
Mateu, Cecilia Gabriela; Artuso, María Carolina; Pujol, Carlos Alberto; Linero, Florencia Natalia; Scolaro, Luis Alberto; et al.; In vitro isolation of variants of herpes simplex virus attenuated with altered thymidine kinase and DNA polymerase genes using carrageenans as selection agents; Springer; Symbiosis; 72; 1; 5-2017; 23-30
0334-5114
CONICET Digital
CONICET
url http://hdl.handle.net/11336/59594
identifier_str_mv Mateu, Cecilia Gabriela; Artuso, María Carolina; Pujol, Carlos Alberto; Linero, Florencia Natalia; Scolaro, Luis Alberto; et al.; In vitro isolation of variants of herpes simplex virus attenuated with altered thymidine kinase and DNA polymerase genes using carrageenans as selection agents; Springer; Symbiosis; 72; 1; 5-2017; 23-30
0334-5114
CONICET Digital
CONICET
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language eng
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info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s13199-016-0437-4
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application/pdf
dc.publisher.none.fl_str_mv Springer
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