Protease-sensitive prion species in neoplastic spleens of prion-infected mice with uncoupling of PrP(Sc) and prion infectivity.
J Gen Virol
; 94(Pt 2): 453-463, 2013 Feb.
Article
de En
| MEDLINE
| ID: mdl-23136363
ABSTRACT
Prion diseases are fatal neurodegenerative disorders. An important step in disease pathophysiology is the conversion of cellular prion protein (PrP(C)) to disease-associated misfolded conformers (PrP(Sc)). These misfolded PrP variants are a common component of prion infectivity and are detectable in diseased brain and lymphoreticular organs such as spleen. In the latter, PrP(Sc) is thought to replicate mainly in follicular dendritic cells within spleen follicles. Although the presence of PrP(Sc) is a hallmark for prion disease and serves as a main diagnostic criterion, in certain instances the amount of PrP(Sc) does not correlate well with neurotoxicity or prion infectivity. Therefore, it has been proposed that prions might be a mixture of different conformers and aggregates with differing properties. This study investigated the impact of disruption of spleen architecture by neoplasia on the abundance of different PrP species in spleens of prion-infected mice. Although follicular integrity was completely disturbed, titres of prion infectivity in neoplastic spleens were not significantly altered, yet no protease-resistant PrP(Sc) was detectable. Instead, unique protease-sensitive prion species could be detected in neoplastic spleens. These results indicate the dissociation of PrP(Sc) and prion infectivity and showed the presence of non-PrP(Sc) PrP species in spleen with divergent biochemical properties that become apparent after tissue architecture disruption.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Peptide hydrolases
/
Rate
/
Tumeurs spléniques
/
Prions
/
Maladies à prions
Type d'étude:
Diagnostic_studies
/
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
J Gen Virol
Année:
2013
Type de document:
Article
Pays d'affiliation:
Allemagne