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Protein Misfolding Cyclic Amplification of Prions
10:12

Protein Misfolding Cyclic Amplification of Prions

Published on: November 7, 2012

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PrPSc formation and clearance as determinants of prion tropism

Ronald A Shikiya1, Katie A Langenfeld1, Thomas E Eckland1

  • 1Department of Medical Microbiology and Immunology, Creighton University, Omaha, Nebraska, United States of America.

Plos Pathogens
|March 30, 2017
PubMed

Insights

The drowsy (DY) prion strain, unlike the hyper (HY) strain, cannot establish infection in lymphoreticular system tissues. This inability is linked to DY PrPSc

Area of Science:

  • Neuroscience
  • Infectious Diseases
  • Molecular Biology

Background:

  • Prion strains exhibit variations in neuropathology, incubation period, clinical presentation, host range, and tissue tropism.
  • Transmissible mink encephalopathy (TME) strains, hyper (HY) and drowsy (DY), differ in tissue tropism and susceptibility to extraneural infection routes.
  • DY TME is notably absent in lymphoreticular system (LRS) tissues, irrespective of the inoculation route.

Purpose of the Study:

  • To investigate the reasons behind DY TME's inability to establish infection in LRS tissues.
  • To determine if the spleen environment can support DY TME formation.
  • To explore the role of PrPSc degradation rates in prion tropism.

Main Methods:

  • Tracking DY TME transport across mucosal epithelia and into draining lymphatic vessels.
  • Performing protein misfolding cyclic amplification (PMCA) using DY PrPSc seeds and spleen homogenate.
  • Comparing the degradation susceptibility of DY PrPSc to PrPSc from other lymphotropic strains.

Main Results:

  • DY TME successfully enters LRS tissues via lymphatic transport, indicating transport is not the limiting factor.
  • The spleen environment supports DY PrPSc formation, albeit at slower rates than lymphotropic strains, ruling out a cofactor deficiency.
  • DY PrPSc demonstrates increased susceptibility to degradation compared to PrPSc from other lymphotropic strains.

Conclusions:

  • The restriction of DY TME pathogenesis in LRS tissues stems from its inability to establish infection, not a transport failure.
  • The spleen can support DY PrPSc formation, suggesting other mechanisms are at play.
  • Differential rates of PrPSc formation and clearance, particularly increased degradation of DY PrPSc, likely influence prion tropism.

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