Saïdi Hela, Nasreddine Nadine, Jenabian Mohammad-Ali, Lecerf Maxime, Schols Dominique, Krief Corinne, Balzarini Jan, Bélec Laurent
Unité INSERM U743, Equipe Immunité et Biothérapie Muqueuse, Centre de Recherches Biomédicales des Cordeliers, Paris, France.
J Transl Med. 2007 Jun 12;5:28. doi: 10.1186/1479-5876-5-28.
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.
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.
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.
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.
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.
植物凝集素，如雪花莲凝集素（GNA）和朱顶红凝集素（HHA），是能够连接甘露糖残基的天然蛋白质，因此可抑制HIV与靶细胞的相互作用。植物凝集素是开发杀微生物剂的候选物质。
在HIV在生殖黏膜水平的两个潜在靶细胞，即上皮细胞和单核细胞衍生树突状细胞（MDDC）的细胞膜水平，评估甘露糖特异性植物凝集素HHA和GNA对HIV的活性。
评估HHA和GNA对HIV吸附于生殖上皮HEC-1A细胞系、HIV通过极化上皮HEC-1A细胞单层的转胞吞作用、HIV吸附于MDDC以及HIV从MDDC转移至自体T淋巴细胞的抑制作用。
HHA以剂量依赖方式微弱抑制R5嗜性HIV-1Ba-L株与HEC-1A细胞的附着，而GNA在相同情况下适度抑制HIV吸附，但仅在高药物剂量时。仅HHA以剂量依赖方式抑制HIV-1JR-CSF的转胞吞作用，而GNA无此作用。通过共聚焦显微镜观察，HHA而非GNA吸附于上皮细胞表面，提示HHA与介导HIV-1转胞吞作用的受体特异性相互作用。两种植物凝集素均部分抑制HIV与MDDC的附着。HHA比GNA更有效地抑制HIV从MDDC向T细胞的转移。无论使用何种细胞系统，HHA和GNA在200μg/ml以下均无毒性，且不破坏上皮细胞的单层完整性。
这些观察结果表明，与GNA相比，凝集素植物HHA在HIV吸附于HEC-1A细胞系、HIV通过HEC-1A细胞系单层的转胞吞作用、HIV吸附于MDDC以及HIV从MDDC转移至T细胞方面具有更高的抑制活性，突出了HHA作为抗HIV有效杀微生物剂的潜在价值。
