Rapid transepithelial transport of prions following inhalation

Anthony E. Kincaid, Kathryn F. Hudson, Matthew W. Richey, Jason C. Bartz

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Prion infection and pathogenesis are dependent on the agent crossing an epithelial barrier to gain access to the recipient nervous system. Several routes of infection have been identified, but the mechanism(s) and timing of in vivo prion transport across an epithelium have not been determined. The hamster model of nasal cavity infection was used to determine the temporal and spatial parameters of prion-infected brain homogenate uptake following inhalation and to test the hypothesis that prions cross the nasal mucosa viaMcells. A small drop of infected or uninfected brain homogenate was placed below each nostril, where it was immediately inhaled into the nasal cavity. Regularly spaced tissue sections through the entire extent of the nasal cavity were processed immunohistochemically to identify brain homogenate and the disease-associated isoform of the prion protein (PrPd). Infected or uninfected brain homogenate was identified adhering toMcells, passing between cells of the nasal mucosa, and within lymphatic vessels of the nasal cavity at all time points examined. PrPd was identified within a limited number ofMcells 15 to 180 min following inoculation, but not in the adjacent nasal mucosa-associated lymphoid tissue (NALT). While these results supportMcell transport of prions, larger amounts of infected brain homogenate were transported paracellularly across the respiratory, olfactory, and follicle-associated epithelia of the nasal cavity. These results indicate that prions can immediately cross the nasal mucosa via multiple routes and quickly enter lymphatics, where they can spread systemically via lymph draining the nasal cavity.

Original languageEnglish (US)
Pages (from-to)12731-12740
Number of pages10
JournalJournal of Virology
Volume86
Issue number23
DOIs
StatePublished - Dec 2012

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Fingerprint Dive into the research topics of 'Rapid transepithelial transport of prions following inhalation'. Together they form a unique fingerprint.

  • Cite this