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Interference in dengue virus adsorption and uncoating by carrageenans.
Virology. 2007 Jul 05; 363(2):473-85.V

Abstract

This study demonstrated that the lambda- and iota-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 microg/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 lambda-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.

Authors+Show Affiliations

Talarico LB
Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Piso 4, 1428 Buenos Aires, Argentina.
Damonte EB
No affiliation info available

MeSH

AnimalsCarrageenanCell LineDengueDengue VirusDose-Response Relationship, DrugHumansVirus Replication

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17337028

Citation

Talarico, Laura B., and Elsa B. Damonte. "Interference in Dengue Virus Adsorption and Uncoating By Carrageenans." Virology, vol. 363, no. 2, 2007, pp. 473-85.
Talarico LB, Damonte EB. Interference in dengue virus adsorption and uncoating by carrageenans. Virology. 2007;363(2):473-85.
Talarico, L. B., & Damonte, E. B. (2007). Interference in dengue virus adsorption and uncoating by carrageenans. Virology, 363(2), 473-85.
Talarico LB, Damonte EB. Interference in Dengue Virus Adsorption and Uncoating By Carrageenans. Virology. 2007 Jul 5;363(2):473-85. PubMed PMID: 17337028.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interference in dengue virus adsorption and uncoating by carrageenans. AU - Talarico,Laura B, AU - Damonte,Elsa B, Y1 - 2007/03/06/ PY - 2007/01/12/received PY - 2007/01/16/accepted PY - 2007/3/6/pubmed PY - 2007/7/7/medline PY - 2007/3/6/entrez SP - 473 EP - 85 JF - Virology JO - Virology VL - 363 IS - 2 N2 - This study demonstrated that the lambda- and iota-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 microg/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 lambda-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. SN - 0042-6822 UR - https://www.unboundmedicine.com/medline/citation/17337028/Interference_in_dengue_virus_adsorption_and_uncoating_by_carrageenans_ DB - PRIME DP - Unbound Medicine ER -