Goldmann C, Petry H, Frye S, Ast O, Ebitsch S, Jentsch K D, Kaup F J, Weber F, Trebst C, Nisslein T, Hunsmann G, Weber T, Lüke W
Department of Virology and Immunology, German Primate Centre, D-37077 Göttingen, Germany.
J Virol. 1999 May;73(5):4465-9. doi: 10.1128/JVI.73.5.4465-4469.1999.
The major structural viral protein, VP1, of the human polyomavirus JC virus (JCV), the causative agent of progressive multifocal leukoencephalopathy (PML), was expressed by using recombinant baculoviruses. Recombinant VP1 formed virus-like particles (VLP) with the typical morphology of empty JCV capsids. Purified VP1 VLP bind to SVG, B, and T cells, as well as to monkey kidney cells. After binding, VP1 VLP were also internalized with high efficiency and transported to the nucleus. Immunization studies revealed these particles as highly immunogenic when administered with adjuvant, while immunization without adjuvant induced no immune response. VP1 VLP hyperimmune serum inhibits binding to SVG cells and neutralizes natural JCV. Furthermore, the potential of VP1 VLP as an efficient transporter system for gene therapy was demonstrated. Exogenous DNA could be efficiently packaged into VP1 VLP, and the packaged DNA was transferred into COS-7 cells as shown by the expression of a marker gene. Thus, VP1 VLP are useful for PML vaccine development and represent a potential new transporter system for human gene therapy.
人多瘤病毒JC病毒（JCV）是进行性多灶性白质脑病（PML）的病原体，其主要结构病毒蛋白VP1通过重组杆状病毒进行表达。重组VP1形成了具有空JCV衣壳典型形态的病毒样颗粒（VLP）。纯化的VP1 VLP可与SVG、B和T细胞以及猴肾细胞结合。结合后，VP1 VLP也能高效内化并转运至细胞核。免疫研究表明，这些颗粒与佐剂一起给药时具有高度免疫原性，而无佐剂免疫则不诱导免疫反应。VP1 VLP超免疫血清可抑制与SVG细胞的结合并中和天然JCV。此外，还证明了VP1 VLP作为基因治疗有效转运系统的潜力。外源DNA可有效包装到VP1 VLP中，如标记基因的表达所示，包装的DNA被转移到COS-7细胞中。因此，VP1 VLP可用于PML疫苗开发，并代表了一种潜在的人类基因治疗新转运系统。
