Chander R, Schreier H
Department of Pharmaceutics Drug Delivery Laboratory, University of Florida Progress Center, Alachua 32615.
Life Sci. 1992;50(7):481-9. doi: 10.1016/0024-3205(92)90387-5.
An artificial viral envelope was constructed, resembling the human immunodeficiency virus (HIV) envelope with respect to ultrastructure, size, phospholipid profile and lipid:cholesterol ratio. Recombinant HIV surface protein gp160 was anchored in the outer surface of the envelope membrane using a double detergent dialysis. The envelopes remained physically stable for several months. Immunolabeling with anti-gp160/41 monoclonal antibody revealed surface insertion and availability of gp160 for binding. Cell fusion and cytosolic transfer of the encapsulated fluorescent marker FITC-dextran was demonstrated. Flow cytometry indicated more efficient transfer of the fluorescent marker to cells which were approximately 60% CD4+ (REX-1B), relative to cells which were only approximately 18% CD4+ (KG-1). However, plain lipid envelopes without gp160 fused very efficiently with both cell types, indicating their potential usefulness as "fusogenic liposomes". Complete artificial viral envelopes may serve as subunit vaccines, and receptor-targeted delivery systems for drugs, toxins and genetic constructs.
构建了一种人工病毒包膜,其在超微结构、大小、磷脂谱和脂质与胆固醇比例方面类似于人类免疫缺陷病毒(HIV)包膜。使用双去污剂透析法将重组HIV表面蛋白gp160锚定在包膜膜的外表面。这些包膜在物理上保持稳定数月。用抗gp160/41单克隆抗体进行免疫标记显示gp160在表面插入且可用于结合。证明了封装的荧光标记物FITC-葡聚糖的细胞融合和胞质转移。流式细胞术表明,相对于仅约18% CD4+的细胞(KG-1),荧光标记物向约60% CD4+的细胞(REX-1B)的转移更有效。然而,没有gp160的普通脂质包膜与两种细胞类型都非常有效地融合,表明它们作为“融合脂质体”的潜在用途。完整的人工病毒包膜可作为亚单位疫苗,以及用于药物、毒素和基因构建体的受体靶向递送系统。