Differential in vitro inhibitory activity against HIV-1 of alpha-(1-3)- and alpha-(1-6)-D-mannose specific plant lectins : Implication for microbicide development

Hela Saïdi,Dominique Schols,Corinne Krief,Laurent Bélec,Jan Balzarini,Nadine Nasreddine,Mohammad-Ali Jenabian,Maxime Lecerf

doi:10.1186/1479-5876-5-28

Abstract

BackgroundPlant lectins such as Galanthus nivalis agglutinin (GNA) and Hippeastrum hybrid agglutinin (HHA) are natural proteins able to link mannose residues, and therefore inhibit HIV-target cell interactions. Plant lectins are candidate for microbicide development.ObjectiveTo evaluate the activity against HIV of the mannose-specific plant lectins HHA and GNA at the cellular membrane level of epithelial cells and monocyte-derived dendritic cells (MDDC), two potential target cells of HIV at the genital mucosal level.MethodsThe inhibitory effects of HHA and GNA were evaluated on HIV adsorption to genital epithelial HEC-1A cell line, on HIV transcytosis throughout a monolayer of polarized epithelial HEC-1A cells, on HIV adsorption to MDDC and on transfer of HIV from MDDC to autologous T lymphocytes.ResultsHHA faintly inhibited attachment to HEC-1A cells of the R5-tropic HIV-1Ba-L strain, in a dose-dependent manner, whereas GNA moderately inhibited HIV adsorption in the same context, but only at high drug doses. Only HHA, but not GNA, inhibited HIV-1JR-CSF transcytosis in a dose-dependent manner. By confocal microscopy, HHA, but not GNA, was adsorbed at the epithelial cell surface, suggesting that HHA interacts specifically with receptors mediating HIV-1 transcytosis. Both plant lectins partially inhibited HIV attachment to MDDC. HHA inhibited more efficiently the transfer of HIV from MDDC to T cell, than GNA. Both HHA and GNA lacked toxicity below 200 μg/ml irrespective the cellular system used and do not disturb the monolayer integrity of epithelial cells.ConclusionThese observations demonstrate higher inhibitory activities of the lectin plant HHA by comparison to GNA, on HIV adsorption to HEC-1A cell line, HIV transcytosis through HEC-1A cell line monolayer, HIV adsorption to MDDC and HIV transfer from MDDC to T cells, highlighting the potential interest of HHA as effective microbicide against HIV.

Highlights

Plant lectins such as Galanthus nivalis agglutinin (GNA) and Hippeastrum hybrid agglutinin (HHA) are natural proteins able to link mannose residues, and inhibit HIV-target cell interactions
HHA and GNA activities in the epithelial cell line HEC-1A (i) Toxicity Any topical microbicide approved for human use first need to be evaluated for epithelial toxicity, because of the direct contact between the product and the vaginal mucosal surface
Non-toxic concentrations of the plant lectins were determined by culturing the epithelial cell line, HEC-1A, for 24 h in the presence of different lectin concentrations (1 Pg/ml to 200 Pg/ml) or medium (Fig. 1A)

Summary

Introduction

Plant lectins such as Galanthus nivalis agglutinin (GNA) and Hippeastrum hybrid agglutinin (HHA) are natural proteins able to link mannose residues, and inhibit HIV-target cell interactions. Galanthus nivalis agglutinin (Snowdrop) (GNA) has specificity for terminal α(1–3)-linked mannose residues, whereas Hippeastrum hybrid agglutinin (Amaryllis) (HHA) recognizes both terminal and internal α(1–3)- and α(1–6)-linked mannose residues [4]. These lectins occur as tetramers exhibiting a molecular mass of 50 kDa. These lectins occur as tetramers exhibiting a molecular mass of 50 kDa They are potent and highly selective inhibitors of the spread of HIV by virus- to- lymphocytes, as well as infected lymphocytes- to- uninfected lymphocytes. HHA and GNA are perfectly fitted to microbicide guidelines in the way they are odorless, tasteless, colorless, not mitogenic and not anti-metabolically active at anti-viral concentrations [4]

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Conclusion