Tags

Type your tag names separated by a space and hit enter

Broad antiviral activity of carbohydrate-binding agents against the four serotypes of dengue virus in monocyte-derived dendritic cells.
PLoS One. 2011; 6(6):e21658.Plos

Abstract

BACKGROUND

Dendritic cells (DC), present in the skin, are the first target cells of dengue virus (DENV). Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) is present on DC and recognizes N-glycosylation sites on the E-glycoprotein of DENV. Thus, the DC-SIGN/E-glycoprotein interaction can be considered as an important target for inhibitors of viral replication. We evaluated various carbohydrate-binding agents (CBAs) against all four described serotypes of DENV replication in Raji/DC-SIGN(+) cells and in monocyte-derived DC (MDDC).

METHODOLOGY/PRINCIPAL FINDINGS

A dose-dependent anti-DENV activity of the CBAs Hippeastrum hybrid (HHA), Galanthus nivalis (GNA) and Urtica dioica (UDA), but not actinohivin (AH) was observed against all four DENV serotypes as analyzed by flow cytometry making use of anti-DENV antibodies. Remarkably, the potency of the CBAs against DENV in MDDC cultures was significantly higher (up to 100-fold) than in Raji/DC-SIGN(+) cells. Pradimicin-S (PRM-S), a small-size non-peptidic CBA, exerted antiviral activity in MDDC but not in Raji/DC-SIGN(+) cells. The CBAs act at an early step of DENV infection as they bind to the viral envelope of DENV and subsequently prevent virus attachment. Only weak antiviral activity of the CBAs was detected when administered after the virus attachment step. The CBAs were also able to completely prevent the cellular activation and differentiation process of MDDC induced upon DENV infection.

CONCLUSIONS/SIGNIFICANCE

The CBAs exerted broad spectrum antiviral activity against the four DENV serotypes, laboratory-adapted viruses and low passage clinical isolates, evaluated in Raji/DC-SIGN(+) cells and in primary MDDC.

Links

PMC Free PDF
PMC Free Full Text
FREE Publisher Full Text

Authors+Show Affiliations

Alen MM
Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium.
De Burghgraeve T
No affiliation info available
Kaptein SJ
No affiliation info available
Balzarini J
No affiliation info available
Neyts J
No affiliation info available
Schols D
No affiliation info available

MeSH

Antiviral AgentsCells, CulturedDendritic CellsDengue VirusHumansMonocytes

Pub Type(s)

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

Language

eng

PubMed ID

21738755

Citation

Alen, Marijke M F., et al. "Broad Antiviral Activity of Carbohydrate-binding Agents Against the Four Serotypes of Dengue Virus in Monocyte-derived Dendritic Cells." PloS One, vol. 6, no. 6, 2011, pp. e21658.
Alen MM, De Burghgraeve T, Kaptein SJ, et al. Broad antiviral activity of carbohydrate-binding agents against the four serotypes of dengue virus in monocyte-derived dendritic cells. PLoS One. 2011;6(6):e21658.
Alen, M. M., De Burghgraeve, T., Kaptein, S. J., Balzarini, J., Neyts, J., & Schols, D. (2011). Broad antiviral activity of carbohydrate-binding agents against the four serotypes of dengue virus in monocyte-derived dendritic cells. PloS One, 6(6), e21658. https://doi.org/10.1371/journal.pone.0021658
Alen MM, et al. Broad Antiviral Activity of Carbohydrate-binding Agents Against the Four Serotypes of Dengue Virus in Monocyte-derived Dendritic Cells. PLoS One. 2011;6(6):e21658. PubMed PMID: 21738755.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Broad antiviral activity of carbohydrate-binding agents against the four serotypes of dengue virus in monocyte-derived dendritic cells. AU - Alen,Marijke M F, AU - De Burghgraeve,Tine, AU - Kaptein,Suzanne J F, AU - Balzarini,Jan, AU - Neyts,Johan, AU - Schols,Dominique, Y1 - 2011/06/30/ PY - 2011/01/14/received PY - 2011/06/07/accepted PY - 2011/7/9/entrez PY - 2011/7/9/pubmed PY - 2011/12/13/medline SP - e21658 EP - e21658 JF - PloS one JO - PLoS One VL - 6 IS - 6 N2 - BACKGROUND: Dendritic cells (DC), present in the skin, are the first target cells of dengue virus (DENV). Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) is present on DC and recognizes N-glycosylation sites on the E-glycoprotein of DENV. Thus, the DC-SIGN/E-glycoprotein interaction can be considered as an important target for inhibitors of viral replication. We evaluated various carbohydrate-binding agents (CBAs) against all four described serotypes of DENV replication in Raji/DC-SIGN(+) cells and in monocyte-derived DC (MDDC). METHODOLOGY/PRINCIPAL FINDINGS: A dose-dependent anti-DENV activity of the CBAs Hippeastrum hybrid (HHA), Galanthus nivalis (GNA) and Urtica dioica (UDA), but not actinohivin (AH) was observed against all four DENV serotypes as analyzed by flow cytometry making use of anti-DENV antibodies. Remarkably, the potency of the CBAs against DENV in MDDC cultures was significantly higher (up to 100-fold) than in Raji/DC-SIGN(+) cells. Pradimicin-S (PRM-S), a small-size non-peptidic CBA, exerted antiviral activity in MDDC but not in Raji/DC-SIGN(+) cells. The CBAs act at an early step of DENV infection as they bind to the viral envelope of DENV and subsequently prevent virus attachment. Only weak antiviral activity of the CBAs was detected when administered after the virus attachment step. The CBAs were also able to completely prevent the cellular activation and differentiation process of MDDC induced upon DENV infection. CONCLUSIONS/SIGNIFICANCE: The CBAs exerted broad spectrum antiviral activity against the four DENV serotypes, laboratory-adapted viruses and low passage clinical isolates, evaluated in Raji/DC-SIGN(+) cells and in primary MDDC. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/21738755/Broad_antiviral_activity_of_carbohydrate_binding_agents_against_the_four_serotypes_of_dengue_virus_in_monocyte_derived_dendritic_cells_ L2 - https://dx.plos.org/10.1371/journal.pone.0021658 DB - PRIME DP - Unbound Medicine ER -