Cell models of prion infection

Vilette, Didier

doi:10.1051/vetres:2007049

Cited by 77 publications

(77 citation statements)

References 151 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The wild-type and mutant PrP constructs were stably expressed in RK13 cells, a rabbit kidney epithelial cell line, and this cell lineage was chosen because it does not express detectable levels of the endogenous prion protein but is capable of propagating prion infection when transfected with murine or ovine PrP (13,22). Transfected RK13 cell lines were shown to stably express wild-type or mutant PrP as detected by Western blot analysis, and all mutants appeared to show similar glycosylation, although PrP C expression varied between cell lines ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Conservation of a Glycine-rich Region in the Prion Protein Is Required for Uptake of Prion Infectivity

Harrison

Lawson

Coleman

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

Prion diseases are associated with the misfolding of the endogenously expressed prion protein (designated PrP C ) into an abnormal isoform (PrP Sc ) that has infectious properties. The hydrophobic domain of PrP C is highly conserved and contains a series of glycine residues that show perfect conservation among all species, strongly suggesting it has functional and evolutionary significance. These glycine residues appear to form repeats of the GXXXG protein-protein interaction motif (two glycines separated by any three residues); the retention of these residues is significant and presumably relates to the functionality of PrP C . Mutagenesis studies demonstrate that minor alterations to this highly conserved region of PrP C drastically affect the ability of cells to uptake and replicate prion infection in both cell and animal bioassay. The localization and processing of mutant PrP C are not affected, although in vitro and in vivo studies demonstrate that this region is not essential for interaction with PrP Sc , suggesting these residues provide conformational flexibility. These data suggest that this region of PrP C is critical in the misfolding process and could serve as a novel, species-independent target for prion disease therapeutics.

show abstract

Section: Resultsmentioning

confidence: 99%

Conservation of a Glycine-rich Region in the Prion Protein Is Required for Uptake of Prion Infectivity

Harrison

Lawson

Coleman

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…10, 11) or is a side effect of neurodegenerative change. We explored this possibility using monocultures of cells that lack pathological signs upon prion infection (30). First, we compared N2a neuroblastoma expressing mouse PrP C -A (N2a) (31) and rabbit RK13-Gag cells expressing elk PrP C (RK13 Elk21) (32) chronically infected with RML prions or elk CWD prions, respectively.…”

Section: Figurementioning

confidence: 99%

Prion disease tempo determined by host-dependent substrate reduction

Mays¹,

Kim²,

Haldiman³

et al. 2014

J. Clin. Invest.

View full text Add to dashboard Cite

The symptoms of prion infection can take years or decades to manifest following the initial exposure. Molecular markers of prion disease include accumulation of the misfolded prion protein (PrP Sc ), which is derived from its cellular precursor (PrP C ), as well as downregulation of the PrP-like Shadoo (Sho) glycoprotein. Given the overlapping cellular environments for PrP C and Sho, we inferred that PrP C levels might also be altered as part of a host response during prion infection. Using rodent models, we found that, in addition to changes in PrP C glycosylation and proteolytic processing, net reductions in PrP C occur in a wide range of prion diseases, including sheep scrapie, human Creutzfeldt-Jakob disease, and cervid chronic wasting disease. The reduction in PrP C results in decreased prion replication, as measured by the protein misfolding cyclic amplification technique for generating PrP Sc in vitro. While PrP C downregulation is not discernible in animals with unusually short incubation periods and high PrP C expression, slowly evolving prion infections exhibit downregulation of the PrP C substrate required for new PrP Sc synthesis and as a receptor for pathogenic signaling. Our data reveal PrP C downregulation as a previously unappreciated element of disease pathogenesis that defines the extensive, presymptomatic period for many prion strains.

show abstract

“…25 Similarly, Rov9 cells were shown to be highly permissive to mouse-passaged classical ovine scrapie prion isolates. 11,12 A previous study by our group 21 used bioassay in Tg338 mice to characterize classical scrapie from a goat with PRNP haplotype 1,2 (animal ID: g3538), haplotype 2,3 (animal IDs: g30-75) or haplotype 1,4 (animal ID: g3558).…”

Section: Cprk13 Cells Support Propagation Of Tg338 Mouse-passaged Prnmentioning

confidence: 98%

A transfectant RK13 cell line permissive to classical caprine scrapie prion propagation

Dassanayake

Zhuang

Truscott

et al. 2016

Prion

View full text Add to dashboard Cite

ABSTRACT. To assess scrapie infectivity associated with caprine-origin tissues, bioassay can be performed using kids, lambs or transgenic mice expressing caprine or ovine prion (PRNP) alleles, but the incubation periods are fairly long. Although several classical ovine scrapie prion permissive cell lines with the ability to detect brain-derived scrapie prion have been available, no classical caprine scrapie permissive cell line is currently available. Therefore, the aims of this study were to generate a rabbit kidney epithelial cell line (RK13) stably expressing caprine wild-type PRNP (cpRK13) and then to assess permissiveness of cpRK13 cells to classical caprine scrapie prion propagation. The cpRK13 and plasmid control RK13 (pcRK13) cells were incubated with brain-derived classical caprine scrapie inocula prepared from goats or ovinized transgenic mice (Tg338, express ovine VRQ allele) infected with caprine scrapie. Significant PrP Sc accumulation, which is indicative of scrapie prion propagation, was detected by TSE ELISA and immunohistochemistry in cpRK13 cells inoculated with classical caprine scrapie inocula. Western blot analysis revealed the typical proteinase K-resistant 3 PrP res isoforms in the caprine scrapie prion inoculated cpRK13 cell lysate. Importantly, PrP Sc accumulation was not detected in similarly inoculated pcRK13 cells, whether by TSE ELISA, immunohistochemistry, or western blot. These findings suggest that caprine scrapie prions can be propagated in cpRK13 cells, thus this cell line may be a useful tool for the assessment of classical caprine prions in the brain tissues of goats.

show abstract

Cell models of prion infection

Cited by 77 publications

References 151 publications

Conservation of a Glycine-rich Region in the Prion Protein Is Required for Uptake of Prion Infectivity

Conservation of a Glycine-rich Region in the Prion Protein Is Required for Uptake of Prion Infectivity

Prion disease tempo determined by host-dependent substrate reduction

A transfectant RK13 cell line permissive to classical caprine scrapie prion propagation

Contact Info

Product

Resources

About