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Biochemical properties of highly neuroinvasive prion strains.

ABSTRACT: Infectious prions propagate from peripheral entry sites into the central nervous system (CNS), where they cause progressive neurodegeneration that ultimately leads to death. Yet the pathogenesis of prion disease can vary dramatically depending on the strain, or conformational variant of the aberrantly folded and aggregated protein, PrP(Sc). Although most prion strains invade the CNS, some prion strains cannot gain entry and do not cause clinical signs of disease. The conformational basis for this remarkable variation in the pathogenesis among strains is unclear. Using mouse-adapted prion strains, here we show that highly neuroinvasive prion strains primarily form diffuse aggregates in brain and are noncongophilic, conformationally unstable in denaturing conditions, and lead to rapidly lethal disease. These neuroinvasive strains efficiently generate PrP(Sc) over short incubation periods. In contrast, the weakly neuroinvasive prion strains form large fibrillary plaques and are stable, congophilic, and inefficiently generate PrP(Sc) over long incubation periods. Overall, these results indicate that the most neuroinvasive prion strains are also the least stable, and support the concept that the efficient replication and unstable nature of the most rapidly converting prions may be a feature linked to their efficient spread into the CNS.

SUBMITTER: Bett C

PROVIDER: S-EPMC3271082 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Biochemical properties of highly neuroinvasive prion strains.

Bett Cyrus C Joshi-Barr Shivanjali S Lucero Melanie M Trejo Margarita M Liberski Pawel P Kelly Jeffery W JW Masliah Eliezer E Sigurdson Christina J CJ

PLoS pathogens 20120202 2

Infectious prions propagate from peripheral entry sites into the central nervous system (CNS), where they cause progressive neurodegeneration that ultimately leads to death. Yet the pathogenesis of prion disease can vary dramatically depending on the strain, or conformational variant of the aberrantly folded and aggregated protein, PrP(Sc). Although most prion strains invade the CNS, some prion strains cannot gain entry and do not cause clinical signs of disease. The conformational basis for thi ...[more]

PMID: 22319450

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Biochemical properties of highly neuroinvasive prion strains.

Publications

Biochemical properties of highly neuroinvasive prion strains.

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