Molecular cloning and expression of major structural protein VP1 of the human polyomavirus JC virus: Formation of virus-like particles useful for immunological and therapeutic studies

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 for med virus-like particles (VLP) with the typical morphology of empty JCV cap sids, Purified VP1 VLP bind to SVG, B, and T cells, as well as to monkey ki dney cells. After binding, VP1 VLP were also internalized with high efficie ncy and transported to the nucleus, Immunization studies revealed these par ticles as highly immunogenic when administered,vith adjuvant, while immuniz ation without adjuvant induced no immune response. VP1 VLP hyperimmune seru m inhibits binding to SVG cells and neutralizes natural JCV, Furthermore, t he 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 exp ression of a marker gene. Thus, VP1 VLP are useful for PML vaccine developm ent and represent a potential new transporter system for human gene therapy .