Interference in dengue virus adsorption and uncoating by carrageenans

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This study demonstrated that the λ- and ι-carrageenans, sulfated polysaccharides containing linear chains of galactopyranosyl residues, are potent inhibitors of dengue virus type 2 (DENV-2) and 3 (DENV-3) multiplication in Vero and HepG2 cells, with values of effective concentration 50% from 0.14 to...

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Autores principales:	Talarico, L.B., Damonte, E.B.
Formato:	Artículo publishedVersion
Lenguaje:	Inglés
Publicado:	2007
Materias:	Adsorption Carrageenan Dengue virus Flavivirus Heparan sulfate Internalization Uncoating Virus entry antivirus agent carrageenan coat protein heparan sulfate animal cell antigen expression antiviral activity article controlled study dengue dose response dose time effect relation drug inhibition drug structure endosome host cell human human cell internalization macromolecule nonhuman priority journal protein synthesis reverse transcription polymerase chain reaction virion virogenesis virus adsorption virus inhibition virus nucleocapsid Animals Cell Line Dengue Dengue Virus Dose-Response Relationship, Drug Humans Virus Replication Dengue virus type 2
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00426822_v363_n2_p473_Talarico
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paperaa:paper_00426822_v363_n2_p473_Talarico
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spelling	paperaa:paper_00426822_v363_n2_p473_Talarico2023-06-12T16:45:39Z Interference in dengue virus adsorption and uncoating by carrageenans Virology 2007;363(2):473-485 Talarico, L.B. Damonte, E.B. Adsorption Carrageenan Dengue virus Flavivirus Heparan sulfate Internalization Uncoating Virus entry antivirus agent carrageenan coat protein heparan sulfate animal cell antigen expression antiviral activity article controlled study dengue Dengue virus dose response dose time effect relation drug inhibition drug structure endosome Flavivirus host cell human human cell internalization macromolecule nonhuman priority journal protein synthesis reverse transcription polymerase chain reaction virion virogenesis virus adsorption virus inhibition virus nucleocapsid Animals Carrageenan Cell Line Dengue Dengue Virus Dose-Response Relationship, Drug Humans Virus Replication Dengue virus Dengue virus type 2 Flavivirus This study demonstrated that the λ- and ι-carrageenans, sulfated polysaccharides containing linear chains of galactopyranosyl residues, are potent inhibitors of dengue virus type 2 (DENV-2) and 3 (DENV-3) multiplication in Vero and HepG2 cells, with values of effective concentration 50% from 0.14 to 4.1 μg/ml. This activity was assayed by plaque reduction, virus yield inhibition and antigen expression tests, and was independent of the input multiplicity of infection in the range 0.001-1. The inhibitory action of the λ-carrageenan, an heparan sulfate (HS)-imitative compound, was exerted by a dual interference with virus adsorption and internalization of nucleocapsid into the cytoplasm. Although virus particles may enter the cell when compound was added after DENV-2 adsorption, as shown by intracellular uptake of radiolabeled DENV-2 particles and quantitative RT-PCR, infectious center and virion uncoating assays have shown that carrageenan-treated virions cannot be released from the endosomes. Viral protein synthesis, the first step of macromolecular synthesis after DENV entry to the host cell, was not affected by the carrageenan. Furthermore, no inhibition of virus multiplication was detected when the entry process was bypassed through DENV-2 RNA transfection into the cell. The dual sites of action of an HS-like molecule suggest that, at least in monkey kidney and human hepatic cells, the HS residues in the cell membrane appear to act as mediators for DENV-2 entry, an interesting alternative target for flavivirus therapy. © 2007 Elsevier Inc. All rights reserved. Fil:Talarico, L.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Damonte, E.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2007 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00426822_v363_n2_p473_Talarico
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
language	Inglés
orig_language_str_mv	eng
topic	Adsorption Carrageenan Dengue virus Flavivirus Heparan sulfate Internalization Uncoating Virus entry antivirus agent carrageenan coat protein heparan sulfate animal cell antigen expression antiviral activity article controlled study dengue Dengue virus dose response dose time effect relation drug inhibition drug structure endosome Flavivirus host cell human human cell internalization macromolecule nonhuman priority journal protein synthesis reverse transcription polymerase chain reaction virion virogenesis virus adsorption virus inhibition virus nucleocapsid Animals Carrageenan Cell Line Dengue Dengue Virus Dose-Response Relationship, Drug Humans Virus Replication Dengue virus Dengue virus type 2 Flavivirus
spellingShingle	Adsorption Carrageenan Dengue virus Flavivirus Heparan sulfate Internalization Uncoating Virus entry antivirus agent carrageenan coat protein heparan sulfate animal cell antigen expression antiviral activity article controlled study dengue Dengue virus dose response dose time effect relation drug inhibition drug structure endosome Flavivirus host cell human human cell internalization macromolecule nonhuman priority journal protein synthesis reverse transcription polymerase chain reaction virion virogenesis virus adsorption virus inhibition virus nucleocapsid Animals Carrageenan Cell Line Dengue Dengue Virus Dose-Response Relationship, Drug Humans Virus Replication Dengue virus Dengue virus type 2 Flavivirus Talarico, L.B. Damonte, E.B. Interference in dengue virus adsorption and uncoating by carrageenans
topic_facet	Adsorption Carrageenan Dengue virus Flavivirus Heparan sulfate Internalization Uncoating Virus entry antivirus agent carrageenan coat protein heparan sulfate animal cell antigen expression antiviral activity article controlled study dengue Dengue virus dose response dose time effect relation drug inhibition drug structure endosome Flavivirus host cell human human cell internalization macromolecule nonhuman priority journal protein synthesis reverse transcription polymerase chain reaction virion virogenesis virus adsorption virus inhibition virus nucleocapsid Animals Carrageenan Cell Line Dengue Dengue Virus Dose-Response Relationship, Drug Humans Virus Replication Dengue virus Dengue virus type 2 Flavivirus
description	This study demonstrated that the λ- and ι-carrageenans, sulfated polysaccharides containing linear chains of galactopyranosyl residues, are potent inhibitors of dengue virus type 2 (DENV-2) and 3 (DENV-3) multiplication in Vero and HepG2 cells, with values of effective concentration 50% from 0.14 to 4.1 μg/ml. This activity was assayed by plaque reduction, virus yield inhibition and antigen expression tests, and was independent of the input multiplicity of infection in the range 0.001-1. The inhibitory action of the λ-carrageenan, an heparan sulfate (HS)-imitative compound, was exerted by a dual interference with virus adsorption and internalization of nucleocapsid into the cytoplasm. Although virus particles may enter the cell when compound was added after DENV-2 adsorption, as shown by intracellular uptake of radiolabeled DENV-2 particles and quantitative RT-PCR, infectious center and virion uncoating assays have shown that carrageenan-treated virions cannot be released from the endosomes. Viral protein synthesis, the first step of macromolecular synthesis after DENV entry to the host cell, was not affected by the carrageenan. Furthermore, no inhibition of virus multiplication was detected when the entry process was bypassed through DENV-2 RNA transfection into the cell. The dual sites of action of an HS-like molecule suggest that, at least in monkey kidney and human hepatic cells, the HS residues in the cell membrane appear to act as mediators for DENV-2 entry, an interesting alternative target for flavivirus therapy. © 2007 Elsevier Inc. All rights reserved.
format	Artículo Artículo publishedVersion
author	Talarico, L.B. Damonte, E.B.
author_facet	Talarico, L.B. Damonte, E.B.
author_sort	Talarico, L.B.
title	Interference in dengue virus adsorption and uncoating by carrageenans
title_short	Interference in dengue virus adsorption and uncoating by carrageenans
title_full	Interference in dengue virus adsorption and uncoating by carrageenans
title_fullStr	Interference in dengue virus adsorption and uncoating by carrageenans
title_full_unstemmed	Interference in dengue virus adsorption and uncoating by carrageenans
title_sort	interference in dengue virus adsorption and uncoating by carrageenans
publishDate	2007
url	http://hdl.handle.net/20.500.12110/paper_00426822_v363_n2_p473_Talarico
work_keys_str_mv	AT talaricolb interferenceindenguevirusadsorptionanduncoatingbycarrageenans AT damonteeb interferenceindenguevirusadsorptionanduncoatingbycarrageenans
_version_	1769810281122234368

Interference in dengue virus adsorption and uncoating by carrageenans

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