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Journal of Virology, May 1999, p. 4465-4469, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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
Claudia
Goldmann,1
Harald
Petry,1
Stephan
Frye,1,2
Oliver
Ast,1
Susanne
Ebitsch,1
Klaus-Dieter
Jentsch,1
Franz-Josef
Kaup,3
Frank
Weber,2
Corinna
Trebst,2
Thomas
Nisslein,1
Gerhard
Hunsmann,1
Thomas
Weber,2,
and
Wolfgang
Lüke1,*
Department of Virology and
Immunology1 and Department of
Experimental Pathology,3 German Primate Centre,
and Department of Neurology, University of
Göttingen,2 D-37077 Göttingen,
Germany
Received 23 April 1997/Accepted 1 February 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.
*
Corresponding author. Mailing address: Department of
Virology and Immunology, German Primate Centre, Kellnerweg 4, D-37077 Göttingen, Germany. Phone: 49-551-3851152. Fax: 49-551-3851184. E-mail: WLUEKE{at}WWW.DPZ.GWDG.DE.
Present address: Neurological Clinic, Marienkrankenhaus, 22087 Hamburg, Germany.
Journal of Virology, May 1999, p. 4465-4469, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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