PrPScformation and clearance as determinants of prion tropism

Ronald A. Shikiya, Katie A. Langenfeld, Thomas E. Eckland, Jonathan Trinh, Sara A M Holec, Candace K. Mathiason, Anthony Kincaid, Jason C. Bartz

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Prion strains are characterized by strain-specific differences in neuropathology but can also differ in incubation period, clinical disease, host-range and tissue tropism. The hyper (HY) and drowsy (DY) strains of hamster-adapted transmissible mink encephalopathy (TME) differ in tissue tropism and susceptibility to infection by extraneural routes of infection. Notably, DY TME is not detected in the secondary lymphoreticular system (LRS) tissues of infected hosts regardless of the route of inoculation. We found that similar to the lymphotropic strain HY TME, DY TME crosses mucosal epithelia, enters draining lymphatic vessels in underlying laminae propriae, and is transported to LRS tissues. Since DY TME causes disease once it enters the peripheral nervous system, the restriction in DY TME pathogenesis is due to its inability to establish infection in LRS tissues, not a failure of transport. To determine if LRS tissues can support DY TME formation, we performed protein misfolding cyclic amplification using DY PrPScas the seed and spleen homogenate as the source of PrPC. We found that the spleen environment can support DY PrPScformation, although at lower rates compared to lymphotropic strains, suggesting that the failure of DY TME to establish infection in the spleen is not due to the absence of a strain-specific conversion cofactor. Finally, we provide evidence that DY PrPScis more susceptible to degradation when compared to PrPScfrom other lymphotrophic strains. We hypothesize that the relative rates of PrPScformation and clearance can influence prion tropism.

Original languageEnglish (US)
Article numbere1006298
JournalPLoS Pathogens
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2017

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Mink
Tropism
Prions
Brain Diseases
Spleen
Infection
Viral Tropism
Lymphatic Vessels
Host Specificity
Peripheral Nervous System
Cricetinae
Seeds
Mucous Membrane
Epithelium

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Shikiya, R. A., Langenfeld, K. A., Eckland, T. E., Trinh, J., Holec, S. A. M., Mathiason, C. K., ... Bartz, J. C. (2017). PrPScformation and clearance as determinants of prion tropism. PLoS Pathogens, 13(3), [e1006298]. https://doi.org/10.1371/journal.ppat.1006298

PrPScformation and clearance as determinants of prion tropism. / Shikiya, Ronald A.; Langenfeld, Katie A.; Eckland, Thomas E.; Trinh, Jonathan; Holec, Sara A M; Mathiason, Candace K.; Kincaid, Anthony; Bartz, Jason C.

In: PLoS Pathogens, Vol. 13, No. 3, e1006298, 01.03.2017.

Research output: Contribution to journalArticle

Shikiya, RA, Langenfeld, KA, Eckland, TE, Trinh, J, Holec, SAM, Mathiason, CK, Kincaid, A & Bartz, JC 2017, 'PrPScformation and clearance as determinants of prion tropism', PLoS Pathogens, vol. 13, no. 3, e1006298. https://doi.org/10.1371/journal.ppat.1006298
Shikiya RA, Langenfeld KA, Eckland TE, Trinh J, Holec SAM, Mathiason CK et al. PrPScformation and clearance as determinants of prion tropism. PLoS Pathogens. 2017 Mar 1;13(3). e1006298. https://doi.org/10.1371/journal.ppat.1006298
Shikiya, Ronald A. ; Langenfeld, Katie A. ; Eckland, Thomas E. ; Trinh, Jonathan ; Holec, Sara A M ; Mathiason, Candace K. ; Kincaid, Anthony ; Bartz, Jason C. / PrPScformation and clearance as determinants of prion tropism. In: PLoS Pathogens. 2017 ; Vol. 13, No. 3.
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