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Journal of Virology, March 2002, p. 2434-2439, Vol. 76, No. 5
0022-538X/02/$04.00+0     DOI: 10.1128/jvi.76.5.2434-2439.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

PrP Expression and Replication by Schwann Cells: Implications in Prion Spreading

*** Jérôme Follet,1,2 Catherine Lemaire-Vieille,1,2 Françoise Blanquet-Grossard,1,2 Valérie Podevin-Dimster,1 Sylvain Lehmann,3 Jean-Paul Chauvin,4 Jean-Pierre Decavel,1 Ruth Varea,5 Jacques Grassi,6 Michel Fontès,7 and Jean-Yves Cesbron1,2*

Laboratoire de Physiopathologie des Encéphalopathies Spongiformes Transmissibles, C.N.R.S. IFR3-Institut de Biologie de Lille-Institut Pasteur de Lille, 59021 Lille Cedex,1 UFR de Médecine de Grenoble, Université Joseph Fourier, 38706 La Tronche Cedex,2 ,2 UMR-6545, Laboratoire de Génétique et de Physiologie du Développement, IBDM-CNRS-INSERM, Université de la Méditerranée, Campus Luminy, 13288 Marseille Cedex 09,4 Service de Pharmacologie et d'Immunologie, CEA-Saclay, 91191 Gif/Yvette,6 INSERM-U491 Génétique médicale et développement, Faculté de Médecine de la Timone, 13358 Marseille, France,7 Departamento de Patologia Animal, Facultad de Veterinaria, 50013 Zaragoza, Spain5

Received 3 August 2001/ Accepted 16 November 2001

Prion infection relies on a continuous chain of PrPc-expressing tissues to spread from peripheral sites to the central nervous system (CNS). Direct neuroinvasion via peripheral nerves has long been considered likely. However, the speed of axonal flow is incompatible with the lengthy delay prior to the detection of PrPSc in the brain. We hypothesized that Schwann cells could be the candidate implicated in this mechanism; for that, it has to express PrPc and to allow PrPSc conversion. We investigated in vivo localization of PrPc in sciatic nerve samples from different strains of mice. We demonstrated that PrPc is mainly localized at the cell membrane of the Schwann cell. We also studied in vitro expression of PrPc in the Schwann cell line MSC-80 and demonstrated that it expresses PrPc at the same location. More specifically, we demonstrated that this glial cell line, when infected in vitro with the mouse Chandler prion strain, both produces the PrPSc till after 18 passages and is able to transmit disease to mice, which then develop the typical signs of prion diseases. It is the first time that infection and replication of PrPSc are shown in a peripheral glial cell line.

* Corresponding author. Mailing address: Université Joseph Fourier, Domaine de la Merci, 38706 La Tronche, France. Phone: (33)4-76-63-74-68. Fax: (33)4-76-63-74-10. E-mail: jean-yves.cesbron{at}ujf-grenoble.fr.

Journal of Virology, March 2002, p. 2434-2439, Vol. 76, No. 5
0022-538X/02/$04.00+0     DOI: 10.1128/jvi.76.5.2434-2439.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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