Transcriptional stability of cultured cells upon prion infection.
Prion infections induce severe disruption of the central nervous system with neuronal vacuolation and extensive glial reactions, and invariably lead to death of affected individuals. The molecular underpinnings of these events are not well understood. To better define the molecular consequences of prion infections, we analyzed the transcriptional response to persistent prion infection in a panel of three murine neural cell lines in vitro. Colony spot immunochemistry assays indicated that 65-100% of cells were infected in each line. Only the Nav1 gene was marginally modulated in one cell line, whereas transcripts previously reported to be derailed in prion-infected cells were not confirmed in the present study. We attribute these discrepancies to the experimental stringency of the current study, which was performed under conditions designed to minimize potential genetic drifts. These findings are at striking variance with gene expression studies performed on whole brains upon prion infections in vivo, suggesting that many of the latter changes represent secondary reactions to infection. We conclude that, surprisingly, there are no universal transcriptional changes induced by prion infection of neural cells in vitro.
Julius
Christian
C
Institute of Neuropathology, University Hospital of Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.
Hutter
Gregor
G
Wagner
Ulrich
U
Seeger
Harald
H
Kana
Veronika
V
Kranich
Jan
J
Klöhn
Peter-Christian
PC
Klöhn
Peter
P
Weissmann
Charles
C
Miele
Gino
G
Aguzzi
Adriano
A
D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002460:Cell Line; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D007031:Hypothalamus / Q000166:cytology; D007150:Immunohistochemistry; D051379:Mice; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000821:virology; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism; D017096:Prion Diseases / Q000821:virology*; D011328:Prions / Q000235:genetics* / Q000472:pathogenicity; D018075:RNA, Complementary / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D018620:PrPSc Proteins; D011328:Prions; D018075:RNA, Complementary; D012333:RNA, Messenger