Cultured peripheral neuroglial cells are highly permissive to sheep prion infection.
Transmissible spongiform encephalopathies arise as a consequence of infection of the central nervous system (CNS) by prions. Spreading of the infectious agent through the peripheral nervous system (PNS) may represent a crucial step toward CNS neuroinvasion, but the modalities of this process have yet to be clarified. Here we provide further evidence that PNS glial cells are likely targets for infection by prions. Glial cell clones originating from dorsal root ganglia of transgenic mice expressing ovine PrP (tgOv) and simian virus 40 T antigen were found to be readily infectible by sheep scrapie agent. This led us to establish two stable cell lines that exhibited features of Schwann cells. These cells were shown to sustain an efficient and stable replication of sheep prion based on the high level of accumulation of abnormal PrP and infectivity in exposed cultures. We also provide evidence for abnormal PrP deposition in peripheral neuroglial cells from scrapie-infected tgOv mice and sheep. These findings have potential implications in terms of designing new cell systems permissive to prions and of peripheral pathobiology of prion infections.
Archer
Fabienne
F
Unité de Virologie Immunologie Moléculaires, INRA, Jouy-en-Josas, France.
Bachelin
Corinne
C
Andreoletti
Olivier
O
Besnard
Nathalie
N
Perrot
Gregory
G
Langevin
Christelle
C
Le Dur
Annick
A
Vilette
Didier
D
Baron-Van Evercooren
Anne
A
Vilotte
Jean-Luc
JL
Laude
Hubert
H
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D017933:Peripheral Nervous System / Q000378:metabolism; D018621:PrPC Proteins / Q000378:metabolism; D018620:PrPSc Proteins / Q000378:metabolism / Q000472:pathogenicity*; D012583:Schwann Cells / Q000378:metabolism; D012608:Scrapie; D012756:Sheep
D018621:PrPC Proteins; D018620:PrPSc Proteins