Biosynthesis of the Scrapie Prion Protein in Scrapie-Infected Cells

1993 ◽  
pp. 199-200
Author(s):  
A. Taraboulos ◽  
D. R. Borchelt ◽  
A. Raeber ◽  
D. Avrahami ◽  
S. B. Prusiner
Keyword(s):  
Prion Protein ◽  
Infected Cells

The inhibitory effect of the ScFv of an anti-prion protein antibody secreted from N2a58 cells on abnormal prion protein accumulation in scrapie-infected cells, ScN2a

Prions ◽  
2006 ◽  
pp. 255-255
Author(s):  
Yoshihisa Shimizu ◽  
Yuko Kaku-Ushiki ◽  
Shigeo Fukuda ◽  
Morikazu Shinagawa ◽  
Takashi Yokoyama ◽  
...  
Keyword(s):  
Prion Protein ◽  
Inhibitory Effect ◽  
Protein Accumulation ◽  
Infected Cells

scholarly journals Neurotropic influenza A virus infection causes prion protein misfolding into infectious prions in neuroblastoma cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hideyuki Hara ◽  
Junji Chida ◽  
Keiji Uchiyama ◽  
Agriani Dini Pasiana ◽  
Etsuhisa Takahashi ◽  
...  
Keyword(s):  
Prion Protein ◽  
Influenza A Virus ◽  
Protein Misfolding ◽  
Influenza A ◽  
Prion Diseases ◽  
Neuroblastoma Cells ◽  
Cellular Prion Protein ◽  
Infected Cells ◽  
Hit And Run

AbstractMisfolding of the cellular prion protein, PrPC, into the amyloidogenic isoform, PrPSc, which forms infectious protein aggregates, the so-called prions, is a key pathogenic event in prion diseases. No pathogens other than prions have been identified to induce misfolding of PrPC into PrPSc and propagate infectious prions in infected cells. Here, we found that infection with a neurotropic influenza A virus strain (IAV/WSN) caused misfolding of PrPC into PrPSc and generated infectious prions in mouse neuroblastoma cells through a hit-and-run mechanism. The structural and biochemical characteristics of IAV/WSN-induced PrPSc were different from those of RML and 22L laboratory prions-evoked PrPSc, and the pathogenicity of IAV/WSN-induced prions were also different from that of RML and 22L prions, suggesting IAV/WSN-specific formation of PrPSc and infectious prions. Our current results may open a new avenue for the role of viral infection in misfolding of PrPC into PrPSc and formation of infectious prions.

scholarly journals HEPES inhibits the conversion of prion protein in cell culture

2011 ◽  
Vol 92 (5) ◽  
pp. 1244-1250 ◽  
Author(s):  
Karine Delmouly ◽  
Maxime Belondrade ◽  
Danielle Casanova ◽  
Ollivier Milhavet ◽  
Sylvain Lehmann
Keyword(s):  
Cell Culture ◽  
Prion Protein ◽  
Cell Biology ◽  
Culture Medium ◽  
Inhibitory Effect ◽  
Live Cells ◽  
Cell Culture Medium ◽  
Dependent Inhibition ◽  
Infected Cells ◽  
Significant Concentration

HEPES is a well-known buffering reagent used in cell-culture medium. Interestingly, this compound is also responsible for significant modifications of biological parameters such as uptake of organic molecules, alteration of oxidative stress mechanisms or inhibition of ion channels. While using cell-culture medium supplemented with HEPES on prion-infected cells, it was noticed that there was a significant concentration-dependent inhibition of accumulation of the abnormal isoform of the prion protein (PrPSc). This effect was present only in live cells and was thought to be related to modification of the PrP environment or biology. These results could modify the interpretation of cell-culture assays of prion therapeutic agents, as well as of previous cell biology results obtained in the field using HEPES buffers. This inhibitory effect of HEPES could also be exploited to prevent contamination or propagation of prions in cell culture.

scholarly journals Lithium induces clearance of protease resistant prion protein in prion-infected cells by induction of autophagy

2009 ◽  
Vol 109 (1) ◽  
pp. 25-34 ◽  
Author(s):  
Andreas Heiseke ◽  
Yasmine Aguib ◽  
Constanze Riemer ◽  
Michael Baier ◽  
Hermann M. Schätzl
Keyword(s):  
Prion Protein ◽  
Infected Cells

scholarly journals Prion Strain-Dependent Differences in Conversion of Mutant Prion Proteins in Cell Culture

2006 ◽  
Vol 80 (16) ◽  
pp. 7854-7862 ◽  
Author(s):  
Ryuichiro Atarashi ◽  
Valerie L. Sim ◽  
Noriyuki Nishida ◽  
Byron Caughey ◽  
Shigeru Katamine
Keyword(s):  
Prion Protein ◽  
Prion Proteins ◽  
Basic Amino Acid ◽  
Inhibitory Effect ◽  
Wild Type ◽  
Prion Strain ◽  
Potent Inhibitory Effect ◽  
Scrapie Strain ◽  
Infected Cells ◽  
Strain Dependent

ABSTRACT Although the protein-only hypothesis proposes that it is the conformation of abnormal prion protein (PrPSc) that determines strain diversity, the molecular basis of strains remains to be elucidated. In the present study, we generated a series of mutations in the normal prion protein (PrPC) in which a single glutamine residue was replaced with a basic amino acid and compared their abilities to convert to PrPSc in cultured neuronal N2a58 cells infected with either the Chandler or 22L mouse-adapted scrapie strain. In mice, these strains generate PrPSc of the same sequence but different conformations, as judged by infrared spectroscopy. Substitutions at codons 97, 167, 171, and 216 generated PrPC that resisted conversion and inhibited the conversion of coexpressed wild-type PrP in both Chandler-infected and 22L-infected cells. Interestingly, substitutions at codons 185 and 218 gave strain-dependent effects. The Q185R and Q185K PrP were efficiently converted to PrPSc in Chandler-infected but not 22L-infected cells. Conversely, Q218R and Q218H PrP were converted only in 22L-infected cells. Moreover, the Q218K PrP exerted a potent inhibitory effect on the conversion of coexpressed wild-type PrP in Chandler-infected cells but had little effect on 22L-infected cells. These results show that two strains with the same PrP sequence but different conformations have differing abilities to convert the same mutated PrPC.

scholarly journals Cells Expressing Anchorless Prion Protein Are Resistant to Scrapie Infection

2009 ◽  
Vol 83 (9) ◽  
pp. 4469-4475 ◽  
Author(s):  
Kristin L. McNally ◽  
Anne E. Ward ◽  
Suzette A. Priola
Keyword(s):  
Transgenic Mice ◽  
Prion Protein ◽  
Prion Diseases ◽  
Transmitted Disease ◽  
Transmissible Spongiform Encephalopathies ◽  
Gpi Anchor ◽  
Spongiform Encephalopathies ◽  
Infected Cells

ABSTRACT The hallmark of transmissible spongiform encephalopathies (TSEs or prion diseases) is the accumulation of an abnormally folded, partially protease-resistant form (PrP-res) of the normal protease-sensitive prion protein (PrP-sen). PrP-sen is attached to the cell membrane by a glycosylphosphatidylinositol (GPI) anchor. In vitro, the anchor and the local membrane environment are important for the conversion of PrP-sen to PrP-res. In vivo, however, the anchor is not necessary because transgenic mice expressing anchorless PrP-sen accumulate PrP-res and replicate infectivity. To clarify the role of the GPI anchor in TSE infection, cells expressing GPI-anchored PrP-sen, anchorless PrP-sen, or both forms of PrP-sen were exposed to the mouse scrapie strain 22L. Cells expressing anchored PrP-sen produced PrP-res after exposure to 22L. Surprisingly, while cells expressing anchorless PrP-sen made anchorless PrP-res in the first 96 h postinfection, no PrP-res was detected at later passes. In contrast, when cells expressing both forms of PrP-sen were exposed to 22L, both anchored and anchorless PrP-res were detected over multiple passes. Consistent with the in vitro data, scrapie-infected cells expressing anchored PrP-sen transmitted disease to mice whereas cells expressing anchorless PrP-sen alone did not. These results demonstrate that the GPI anchor on PrP-sen is important for the persistent infection of cells in vitro. Our data suggest that cells expressing anchorless PrP-sen are not directly infected with scrapie. Thus, PrP-res formation in transgenic mice expressing anchorless PrP-sen may be occurring extracellularly.

Antibodies to a Nonconjugated Prion Protein Peptide 95-123 Interfere with PrP Sc Propagation in Prion-Infected Cells

2007 ◽  
Vol 27 (3) ◽  
pp. 271-284 ◽  
Author(s):  
Maria B. Oboznaya ◽  
Sabine Gilch ◽  
Maia A. Titova ◽  
Dmitry O. Koroev ◽  
Tatyana D. Volkova ◽  
...  
Keyword(s):  
Prion Protein ◽  
Infected Cells ◽  
Prion Protein Peptide
Sign in / Sign up

Export Citation Format

Share Document