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Cell-specific susceptibility to prion strains is a property of the intact cell

Maria E Herva1, Charles Weissman

  • 1Department of Infectology, Scripps Florida, Jupiter, FL, USA.

Prion
|May 8, 2012
PubMed

Insights

Cellular prion strain susceptibility is determined by the intact cell, not just its protein components. This finding impacts understanding prion diseases and cellular resistance mechanisms.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Infectious Diseases

Background:

  • Prions are misfolded proteins (PrPSc) causing neurodegenerative diseases.
  • Prion strains, differing in phenotype, are linked to PrPSc conformation.
  • Cellular susceptibility to prion strains is not fully understood.

Purpose of the Study:

  • To investigate the basis of cellular susceptibility to prion strains.
  • To determine if cellular components or the intact cell dictates prion susceptibility.

Main Methods:

  • Compared prion amplification using Protein Misfolding Cyclic Amplification (PMCA).
  • Utilized cell lysates from prion-resistant and prion-susceptible cell lines as substrate.
  • Assessed amplification of Rocky Mountain Laboratory (RML) prions.

Main Results:

  • Both resistant and susceptible cell lysates equally supported RML prion amplification.
  • A 280-fold difference in cellular susceptibility did not affect in vitro amplification.
  • Prion amplification in vitro is independent of the cell's in vivo susceptibility.

Conclusions:

  • Cellular susceptibility to prion strains is an attribute of the intact cell, not isolated cellular components.
  • This suggests cell-intrinsic factors beyond PrPSc conformation govern prion tropism and pathogenicity.
  • Further research should focus on intact cell models to understand prion-cell interactions.

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