Characterization of in vitro dengue virus resistance to carrageenan
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...
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2016
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Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01466615_v88_n7_p1120_Talarico http://hdl.handle.net/20.500.12110/paper_01466615_v88_n7_p1120_Talarico |
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paper:paper_01466615_v88_n7_p1120_Talarico2023-06-08T15:12:33Z Characterization of in vitro dengue virus resistance to carrageenan Antiviral resistance Carrageenans Dengue virus Sulfated polysaccharides Virus entry ammonium chloride carrageenan dextran sulfate heparin polysaccharide sulfate antivirus agent carrageenan E protein TH Sman, Dengue virus NS1 protein, Dengue virus type 2 viral protein virus envelope protein animal cell antiviral activity antiviral resistance Article conformational transition controlled study dengue Dengue virus Dengue virus 2 gene sequence in vitro study nonhuman phenotype receptor binding Vero cell line virus attachment virus entry virus isolation animal cell line Chlorocebus aethiops Dengue virus drug effects genetics genotype mutation physiology virus genome virus replication Animals Antiviral Agents Carrageenan Cell Line Cercopithecus aethiops Dengue Virus Drug Resistance, Viral Genome, Viral Genotype Mutation Phenotype Vero Cells Viral Envelope Proteins Viral Nonstructural Proteins Viral Proteins Virus Replication 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. © 2016 Wiley Periodicals, Inc. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01466615_v88_n7_p1120_Talarico http://hdl.handle.net/20.500.12110/paper_01466615_v88_n7_p1120_Talarico |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
Antiviral resistance Carrageenans Dengue virus Sulfated polysaccharides Virus entry ammonium chloride carrageenan dextran sulfate heparin polysaccharide sulfate antivirus agent carrageenan E protein TH Sman, Dengue virus NS1 protein, Dengue virus type 2 viral protein virus envelope protein animal cell antiviral activity antiviral resistance Article conformational transition controlled study dengue Dengue virus Dengue virus 2 gene sequence in vitro study nonhuman phenotype receptor binding Vero cell line virus attachment virus entry virus isolation animal cell line Chlorocebus aethiops Dengue virus drug effects genetics genotype mutation physiology virus genome virus replication Animals Antiviral Agents Carrageenan Cell Line Cercopithecus aethiops Dengue Virus Drug Resistance, Viral Genome, Viral Genotype Mutation Phenotype Vero Cells Viral Envelope Proteins Viral Nonstructural Proteins Viral Proteins Virus Replication |
spellingShingle |
Antiviral resistance Carrageenans Dengue virus Sulfated polysaccharides Virus entry ammonium chloride carrageenan dextran sulfate heparin polysaccharide sulfate antivirus agent carrageenan E protein TH Sman, Dengue virus NS1 protein, Dengue virus type 2 viral protein virus envelope protein animal cell antiviral activity antiviral resistance Article conformational transition controlled study dengue Dengue virus Dengue virus 2 gene sequence in vitro study nonhuman phenotype receptor binding Vero cell line virus attachment virus entry virus isolation animal cell line Chlorocebus aethiops Dengue virus drug effects genetics genotype mutation physiology virus genome virus replication Animals Antiviral Agents Carrageenan Cell Line Cercopithecus aethiops Dengue Virus Drug Resistance, Viral Genome, Viral Genotype Mutation Phenotype Vero Cells Viral Envelope Proteins Viral Nonstructural Proteins Viral Proteins Virus Replication Characterization of in vitro dengue virus resistance to carrageenan |
topic_facet |
Antiviral resistance Carrageenans Dengue virus Sulfated polysaccharides Virus entry ammonium chloride carrageenan dextran sulfate heparin polysaccharide sulfate antivirus agent carrageenan E protein TH Sman, Dengue virus NS1 protein, Dengue virus type 2 viral protein virus envelope protein animal cell antiviral activity antiviral resistance Article conformational transition controlled study dengue Dengue virus Dengue virus 2 gene sequence in vitro study nonhuman phenotype receptor binding Vero cell line virus attachment virus entry virus isolation animal cell line Chlorocebus aethiops Dengue virus drug effects genetics genotype mutation physiology virus genome virus replication Animals Antiviral Agents Carrageenan Cell Line Cercopithecus aethiops Dengue Virus Drug Resistance, Viral Genome, Viral Genotype Mutation Phenotype Vero Cells Viral Envelope Proteins Viral Nonstructural Proteins Viral Proteins Virus Replication |
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. © 2016 Wiley Periodicals, Inc. |
title |
Characterization of in vitro dengue virus resistance to carrageenan |
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 |
publishDate |
2016 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01466615_v88_n7_p1120_Talarico http://hdl.handle.net/20.500.12110/paper_01466615_v88_n7_p1120_Talarico |
_version_ |
1768543839910363136 |