TY - JOUR
T1 - Specificity, size, and frequency of spaces that characterize the mechanism of bulk transepithelial transport of prions in the nasal cavities of hamsters and mice
AU - Kincaid, A. E.
AU - Ayers, J. I.
AU - Bartz, J. C.
N1 - Publisher Copyright:
© 2016, American Society for Microbiology. All Rights Reserved.
PY - 2016
Y1 - 2016
N2 - Inhalation of infected brain homogenate results in transepithelial transport of prions across the nasal mucosa of hamsters, some of which occurs rapidly in relatively large amounts between cells (A. E. Kincaid, K. F. Hudson, M. W. Richey, and J. C. Bartz, J. Virol 86:12731-12740, 2012, doi:http://dx.doi.org/10.1128/JVI.01930-12). Bulk transepithelial transport in the nasal cavity has not been studied to date. In the present study, we characterized the frequency, size, and specificity of the intercellular spaces that mediate the bulk transport of inhaled prions between cells of mice or hamsters following extranasal inoculation with mock-infected brain homogenate, different strains of prion-infected brain homogenate, or brain homogenate mixed with India ink. Infected or mock-infected inoculum was identified within lymphatic vessels of the lamina propria and in spaces of >5μm between a small number of cells of the nasal mucosa in >90% of animals from 5 to 60 min after inhalation. The width of the spaces between cells, the amount of the inoculum within the lumen of lymphatic vessels, and the timing of the transport indicate that this type of transport was taking place through preexisting spaces in the nasal cavity that were orders of magnitude wider than what is normally reported for paracellular transport. The indiscriminate rapid bulk transport of brain homogenate in the nasal cavity results in immediate entry into nasal cavity lymphatics following inhalation. This novel mechanism may underlie the recent report of the early detection of prions in blood following inhalation and has implications for horizontal prion transmission.
AB - Inhalation of infected brain homogenate results in transepithelial transport of prions across the nasal mucosa of hamsters, some of which occurs rapidly in relatively large amounts between cells (A. E. Kincaid, K. F. Hudson, M. W. Richey, and J. C. Bartz, J. Virol 86:12731-12740, 2012, doi:http://dx.doi.org/10.1128/JVI.01930-12). Bulk transepithelial transport in the nasal cavity has not been studied to date. In the present study, we characterized the frequency, size, and specificity of the intercellular spaces that mediate the bulk transport of inhaled prions between cells of mice or hamsters following extranasal inoculation with mock-infected brain homogenate, different strains of prion-infected brain homogenate, or brain homogenate mixed with India ink. Infected or mock-infected inoculum was identified within lymphatic vessels of the lamina propria and in spaces of >5μm between a small number of cells of the nasal mucosa in >90% of animals from 5 to 60 min after inhalation. The width of the spaces between cells, the amount of the inoculum within the lumen of lymphatic vessels, and the timing of the transport indicate that this type of transport was taking place through preexisting spaces in the nasal cavity that were orders of magnitude wider than what is normally reported for paracellular transport. The indiscriminate rapid bulk transport of brain homogenate in the nasal cavity results in immediate entry into nasal cavity lymphatics following inhalation. This novel mechanism may underlie the recent report of the early detection of prions in blood following inhalation and has implications for horizontal prion transmission.
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U2 - 10.1128/JVI.01103-16
DO - 10.1128/JVI.01103-16
M3 - Article
C2 - 27384659
AN - SCOPUS:84984614294
VL - 90
SP - 8293
EP - 8301
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 18
ER -