James Graham Brown Cancer Center and Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky, United States of America.
PLoS One. 2011;6(8):e22635. doi: 10.1371/journal.pone.0022635. Epub 2011 Aug 2.
Many natural product-derived lectins such as the red algal lectin griffithsin (GRFT) have potent in vitro activity against viruses that display dense clusters of oligomannose N-linked glycans (NLG) on their surface envelope glycoproteins. However, since oligomannose NLG are also found on some host proteins it is possible that treatment with antiviral lectins may trigger undesirable side effects. For other antiviral lectins such as concanavalin A, banana lectin and cyanovirin-N (CV-N), interactions between the lectin and as yet undescribed cellular moieties have been reported to induce undesirable side effects including secretion of inflammatory cytokines and activation of host T-cells. We show that GRFT, unlike CV-N, binds the surface of human epithelial and peripheral blood mononuclear cells (PBMC) through an exclusively oligosaccharide-dependent interaction. In contrast to several other antiviral lectins however, GRFT treatment induces only minimal changes in secretion of inflammatory cytokines and chemokines by epithelial cells or human PBMC, has no measureable effect on cell viability and does not significantly upregulate markers of T-cell activation. In addition, GRFT appears to retain antiviral activity once bound to the surface of PBMC. Finally, RNA microarray studies show that, while CV-N and ConA regulate expression of a multitude of cellular genes, GRFT treatment effects only minimal alterations in the gene expression profile of a human ectocervical cell line. These studies indicate that GRFT has an outstanding safety profile with little evidence of induced toxicity, T-cell activation or deleterious immunological consequence, unique attributes for a natural product-derived lectin.
许多天然产物衍生的凝集素，如红藻凝集素 griffithsin（GRFT），对表面糖蛋白上具有密集寡甘露糖 N-连接糖基（NLG）簇的病毒具有强大的体外活性。然而，由于寡甘露糖 NLG 也存在于一些宿主蛋白上，因此用抗病毒凝集素治疗可能会引发不良的副作用。对于其他抗病毒凝集素，如伴刀豆球蛋白 A、香蕉凝集素和环孢菌素-N（CV-N），已报道凝集素与尚未描述的细胞成分之间的相互作用会引起不良的副作用，包括炎症细胞因子的分泌和宿主 T 细胞的激活。我们表明，GRFT 与 CV-N 不同，通过完全依赖寡糖的相互作用与人类上皮细胞和外周血单核细胞（PBMC）的表面结合。然而，与其他几种抗病毒凝集素不同，GRFT 处理仅导致上皮细胞或人 PBMC 中炎症细胞因子和趋化因子的分泌发生最小变化，对细胞活力没有可测量的影响，并且不会显著上调 T 细胞激活的标志物。此外，GRFT 一旦与 PBMC 表面结合，似乎仍保留抗病毒活性。最后，RNA 微阵列研究表明，虽然 CV-N 和 ConA 调节多种细胞基因的表达，但 GRFT 处理仅对人宫颈外细胞系的基因表达谱产生最小的改变。这些研究表明，GRFT 具有出色的安全性，几乎没有诱导毒性、T 细胞激活或有害免疫后果的证据，这是一种天然产物衍生的凝集素所具有的独特属性。
