Intrinsic resistance of oligodendrocytes to prion infection.
Within the CNS, the normal form of cellular prion protein (PrP(C)) is expressed on neurons, oligodendrocytes, and astrocytes. The contribution of these cell types to prion replication and pathogenesis is unclear. To assess the role of oligodendrocytes, we expressed PrP(C) under the control of the myelin basic protein (MBP) promoter in mice lacking endogenous PrP(C). PrP(C) was detected in oligodendrocytes and Schwann cells but not in neurons and astrocytes. MBP-PrP mice never developed scrapie after intracerebral, intraperitoneal, or intraocular challenge with scrapie prions. Transgenic brains did not contain protease-resistant prion protein and did not transmit scrapie when inoculated into PrP(C)-overexpressing indicator mice. To investigate whether prion spread within the CNS depends on oligodendrocytic PrP(C), we implanted PrP(C)-overexpressing neuroectodermal grafts into MBP-PrP brains. After intraocular prion inoculation, none of the grafts showed spongiform encephalopathy or prion infectivity. Hence oligodendrocytes do not support cell-autonomous prion replication, establishment of subclinical disease, and neural spread of prions. Prion resistance sets oligodendrocytes aside from both neurons and astrocytes.
Prinz
Marco
M
Institute of Neuropathology, University Hospital of Zürich, CH-8091 Zürich, Switzerland.
Montrasio
Fabio
F
Furukawa
Hisako
H
van der Haar
Marjan E
ME
Schwarz
Petra
P
Rülicke
Thomas
T
Giger
Olivier T
OT
Häusler
Karl-Georg
KG
Perez
Daniel
D
Glatzel
Markus
M
Aguzzi
Adriano
A
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D005260:Female; D006031:Glycosylation; D007113:Immunity, Innate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology*; D009928:Organ Specificity; D018621:PrPC Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018620:PrPSc Proteins / Q000472:pathogenicity*; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism; D012608:Scrapie / Q000209:etiology; D014020:Tissue Extracts / Q000009:adverse effects; D014774:Virulence; D014795:Visual Pathways / Q000378:metabolism
D004676:Myelin Basic Protein; D018621:PrPC Proteins; D018620:PrPSc Proteins; D011993:Recombinant Fusion Proteins; D014020:Tissue Extracts