Coinfecting prion strains compete for a limiting cellular resource

Ronald A. Shikiya, Jacob I. Ayers, Charles R. Schutt, Anthony Kincaid, Jason C. Bartz

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Prion strain interference can influence the emergence of a dominant strain from a mixture; however, the mechanisms underlying prion strain interference are poorly understood. In our model of strain interference, inoculation of the sciatic nerve with the drowsy (DY) strain of the transmissible mink encephalopathy (TME) agent prior to superinfection with the hyper (HY) strain of TME can completely block HY TME from causing disease. We show here that the deposition of PrPSc, in the absence of neuronal loss or spongiform change, in the central nervous system corresponds with the ability of DY TME to block HY TME infection. This suggests that DY TME agent-induced damage is not responsible for strain interference but rather prions compete for a cellular resource. We show that protein misfolding cyclic amplification (PMCA) of DY and HY TME maintains the strain-specific properties of PrPSc and replicates infectious agent and that DY TME can interfere, or completely block, the emergence of HY TME. DY PrPSc does not convert all of the available PrPC to PrPSc in PMCA, suggesting the mechanism of prion strain interference is due to the sequestering of PrPC and/or other cellular components required for prion conversion. The emergence of HY TME in PMCA was controlled by the initial ratio of the TME agents. A higher ratio of DY to HY TME agent is required for complete blockage of HY TME in PMCA compared to several previous in vivo studies, suggesting that HY TME persists in animals coinfected with the two strains. This was confirmed by PMCA detection of HY PrPSc in animals where DY TME had completely blocked HY TME from causing disease.

Original languageEnglish
Pages (from-to)5706-5714
Number of pages9
JournalJournal of Virology
Volume84
Issue number11
DOIs
StatePublished - Jun 2010

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transmissible mink encephalopathy
Mink
Prions
prions
Brain Diseases
PrPSc proteins
crossover interference
Proteins
proteins
PrPSc Proteins

All Science Journal Classification (ASJC) codes

  • Immunology
  • Virology

Cite this

Coinfecting prion strains compete for a limiting cellular resource. / Shikiya, Ronald A.; Ayers, Jacob I.; Schutt, Charles R.; Kincaid, Anthony; Bartz, Jason C.

In: Journal of Virology, Vol. 84, No. 11, 06.2010, p. 5706-5714.

Research output: Contribution to journalArticle

Shikiya, Ronald A. ; Ayers, Jacob I. ; Schutt, Charles R. ; Kincaid, Anthony ; Bartz, Jason C. / Coinfecting prion strains compete for a limiting cellular resource. In: Journal of Virology. 2010 ; Vol. 84, No. 11. pp. 5706-5714.
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