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JVI Accepts, published online ahead of print on 14 February 2007
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J. Virol. doi:10.1128/JVI.02649-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The Nasal Cavity is a Route for Prion Infection in Hamsters

Anthony E. Kincaid* and Jason C. Bartz

Department of Physical Therapy, Department of Biomedical Sciences and Department of Medical Microbiology and Immunology, Creighton University, Omaha, Nebraska 68178

* To whom correspondence should be addressed. Email: akincaid{at}creighton.edu.


   Abstract

Animals that naturally acquire the prion diseases have a well-developed olfactory sense that they utilize for a variety of basic behaviors. To assess the potential for the nasal cavity to serve as a point of entry for prion diseases a small amount of prion-infected brain homogenate was placed inferior to the nostrils of hamsters where it was immediately sniffed into the nasal cavity. Hamsters extranasally inoculated with the HY strain of transmissible mink encephalopathy (TME) agent had an incubation period that was not significantly different from per os inoculation of the same dose of the HY TME agent. However the efficiency of the nasal route of inoculation was determined to be 10-100 times greater based on end-point dilution analysis. Immunohistochemistry on tissues from hamsters killed at 2-week intervals following inoculation was used to identify the disease-associated form of the prion protein (PrPd) to determine the route of prion neuroinvasion. Nasal associated lymphoid tissue and submandibular lymph nodes initially accumulated PrPd as early as 4 weeks post infection. PrPd was first identified in cervical lymph nodes at 8 weeks, the mesenteric lymph nodes, spleen and Peyer's patches at 14 weeks and the tongue 20 weeks after inoculation. Surprisingly, there was no evidence of PrPd in olfactory epithelium or olfactory nerve fascicles at any time after inoculation. Therefore the HY TME agent did not enter the central nervous system via the olfactory nerve, instead PrPd accumulated in elements of the cranial lymphoreticular system prior to neuroinvasion.




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