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.
BACKGROUND
Plant 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.


OBJECTIVE
To 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.


METHODS
The 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.


RESULTS
HHA 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 microg/ml irrespective the cellular system used and do not disturb the monolayer integrity of epithelial cells.


CONCLUSIONS
These 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.
Saïdi
Hela
H
Unité INSERM U743, Equipe Immunité et Biothérapie Muqueuse, Centre de Recherches Biomédicales des Cordeliers, Paris, France. hela.saidi@u430.bhdc.jussieu.fr
Nasreddine
Nadine
N
Jenabian
Mohammad-Ali
MA
Lecerf
Maxime
M
Schols
Dominique
D
Krief
Corinne
C
Balzarini
Jan
J
Bélec
Laurent
L
D000328:Adult; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000821:virology; D015195:Drug Design; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D037241:Mannose-Binding Lectins / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D009000:Monocytes / Q000166:cytology; D008517:Phytotherapy; D037121:Plant Lectins / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D053585:Virus Attachment / Q000187:drug effects
D000890:Anti-Infective Agents; D037241:Mannose-Binding Lectins; D037121:Plant Lectins