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

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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 sim...

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Autores principales: Mateu, C.G., Artuso, M.C., Pujol, C.A., Linero, F.N., Scolaro, L.A., Carlucci, M.J.
Formato: JOUR
Materias:
Carrageenan
Herpesvirus
Mutants
Pathogenicity
Syncytial variant
Virulence
enzyme
experimental study
gene
inhibitor
mutation
pathogenicity
physiological response
polysaccharide
rodent
virulence
virus
Animalia
Herpesviridae
Mus
Simplexvirus
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_03345114_v72_n1_p23_Mateu
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
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spelling todo:paper_03345114_v72_n1_p23_Mateu2023-10-03T15:25:22Z In vitro isolation of variants of herpes simplex virus attenuated with altered thymidine kinase and DNA polymerase genes using carrageenans as selection agents Mateu, C.G. Artuso, M.C. Pujol, C.A. Linero, F.N. Scolaro, L.A. Carlucci, M.J. Carrageenan Herpesvirus Mutants Pathogenicity Syncytial variant Virulence enzyme experimental study gene inhibitor mutation pathogenicity physiological response polysaccharide rodent virulence virus Animalia Herpesviridae Mus Simplexvirus 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. © 2016, Springer Science+Business Media Dordrecht. Fil:Mateu, C.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Artuso, M.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Pujol, C.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Linero, F.N. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Scolaro, L.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Carlucci, M.J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_03345114_v72_n1_p23_Mateu
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic Carrageenan
Herpesvirus
Mutants
Pathogenicity
Syncytial variant
Virulence
enzyme
experimental study
gene
inhibitor
mutation
pathogenicity
physiological response
polysaccharide
rodent
virulence
virus
Animalia
Herpesviridae
Mus
Simplexvirus
spellingShingle Carrageenan
Herpesvirus
Mutants
Pathogenicity
Syncytial variant
Virulence
enzyme
experimental study
gene
inhibitor
mutation
pathogenicity
physiological response
polysaccharide
rodent
virulence
virus
Animalia
Herpesviridae
Mus
Simplexvirus
Mateu, C.G.
Artuso, M.C.
Pujol, C.A.
Linero, F.N.
Scolaro, L.A.
Carlucci, M.J.
In vitro isolation of variants of herpes simplex virus attenuated with altered thymidine kinase and DNA polymerase genes using carrageenans as selection agents
topic_facet Carrageenan
Herpesvirus
Mutants
Pathogenicity
Syncytial variant
Virulence
enzyme
experimental study
gene
inhibitor
mutation
pathogenicity
physiological response
polysaccharide
rodent
virulence
virus
Animalia
Herpesviridae
Mus
Simplexvirus
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. © 2016, Springer Science+Business Media Dordrecht.
format JOUR
author Mateu, C.G.
Artuso, M.C.
Pujol, C.A.
Linero, F.N.
Scolaro, L.A.
Carlucci, M.J.
author_facet Mateu, C.G.
Artuso, M.C.
Pujol, C.A.
Linero, F.N.
Scolaro, L.A.
Carlucci, M.J.
author_sort Mateu, C.G.
title In vitro isolation of variants of herpes simplex virus attenuated with altered thymidine kinase and DNA polymerase genes using carrageenans as selection agents
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
url http://hdl.handle.net/20.500.12110/paper_03345114_v72_n1_p23_Mateu
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