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Abstract:

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.

Registro:

Documento: Artículo
Título:Interference in dengue virus adsorption and uncoating by carrageenans
Autor:Talarico, L.B.; Damonte, E.B.
Filiación:Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Ciudad Univ., Pabellon 2, Piso 4, 1428 Buenos Aires, Argentina
Palabras clave: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
Año:2007
Volumen:363
Número:2
Página de inicio:473
Página de fin:485
DOI: http://dx.doi.org/10.1016/j.virol.2007.01.043
Título revista:Virology
Título revista abreviado:Virology
ISSN:00426822
CODEN:VIRLA
CAS:carrageenan, 9000-07-1, 9049-05-2, 9061-82-9, 9064-57-7; heparan sulfate, 9050-30-0; Carrageenan, 9000-07-1
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00426822_v363_n2_p473_Talarico.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00426822_v363_n2_p473_Talarico

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Citas:

---------- APA ----------
Talarico, L.B. & Damonte, E.B. (2007) . Interference in dengue virus adsorption and uncoating by carrageenans. Virology, 363(2), 473-485.
http://dx.doi.org/10.1016/j.virol.2007.01.043
---------- CHICAGO ----------
Talarico, L.B., Damonte, E.B. "Interference in dengue virus adsorption and uncoating by carrageenans" . Virology 363, no. 2 (2007) : 473-485.
http://dx.doi.org/10.1016/j.virol.2007.01.043
---------- MLA ----------
Talarico, L.B., Damonte, E.B. "Interference in dengue virus adsorption and uncoating by carrageenans" . Virology, vol. 363, no. 2, 2007, pp. 473-485.
http://dx.doi.org/10.1016/j.virol.2007.01.043
---------- VANCOUVER ----------
Talarico, L.B., Damonte, E.B. Interference in dengue virus adsorption and uncoating by carrageenans. Virology. 2007;363(2):473-485.
http://dx.doi.org/10.1016/j.virol.2007.01.043