NICTABA and UDA, two GlcNAc-binding lectins with unique antiviral activity profiles.
OBJECTIVES
This study aimed to assess the antiviral properties of a unique lectin (NICTABA) produced by the tobacco plant, Nicotiana tabacum.


METHODS
Cellular assays were used to investigate the antiviral activity of NICTABA and Urtica dioica agglutinin (UDA). Surface plasmon resonance (SPR) studies were performed to study the sugar specificity and the interactions of both lectins with the envelope glycoproteins of HIV-1.


RESULTS
The N-acetyl-d-glucosamine (GlcNAc)-binding lectins exhibited broad-spectrum activity against several families of enveloped viruses including influenza A/B, Dengue virus type 2, herpes simplex virus types 1 and 2 and HIV-1/2. The IC50 of NICTABA for various HIV-1 strains, clinical isolates and HIV-2 assessed in PBMCs ranged from 5 to 30 nM. Furthermore, NICTABA inhibited syncytium formation between persistently HIV-1-infected T cells and uninfected CD4+ T lymphocytes and prevented DC-SIGN-mediated HIV-1 transmission to CD4+ target T lymphocytes. However, unlike many other antiviral carbohydrate-binding agents (CBAs) described so far, NICTABA did not block HIV-1 capture to DC-SIGN+ cells and it did not interfere with the binding of the human monoclonal antibody 2G12 to gp120. SPR studies with HIV-1 envelope glycoproteins showed that the affinity of NICTABA for gp120 and gp41 was in the low nanomolar range. The specific binding of NICTABA to gp120 could be prevented in the presence of a GlcNAc trimer, but not in the presence of mannose trimers. NICTABA displayed no antiviral activity against non-enveloped viruses.


CONCLUSIONS
Since CBAs possess a high genetic barrier for the development of viral resistance and NICTABA shows a broad antiviral activity profile, this CBA may qualify as a potential antiviral candidate with a pleiotropic mode of action aimed at targeting the entry of enveloped viruses.
['Gordts|Stephanie C|SC|', 'Renders|Marleen|M|', 'Férir|Geoffrey|G|', 'Huskens|Dana|D|', 'Van Damme|Els J M|EJ|', 'Peumans|Willy|W|', 'Balzarini|Jan|J|', 'Schols|Dominique|D|']
D000117:Acetylglucosamine D000373:Agglutinins D000998:Antiviral Agents D006801:Humans D020128:Inhibitory Concentration 50 D037102:Lectins D011485:Protein Binding D020349:Surface Plasmon Resonance D014026:Tobacco D026982:Urtica dioica D014780:Viruses D054299:env Gene Products, Human Immunodeficiency Virus
antiviral peptides broad spectrum glycosylation