Prion Shedding from Olfactory Neurons into Nasal Secretions

PLoS Pathogens

Byron Caughey¹  Jason M. Wilham¹  Diana Lowe²  Harold Shearin²  Scott Martinka²  Ryan Boharski²  James A. Wiley²  Richard A. Bessen² 

[1] Laboratory of Persistent Viral Diseases, National Institute of Allergies and Infectious Diseases, Hamilton, Montana, United States of America;Veterinary Molecular Biology, Montana State University, Bozeman, Montana, United States of America

关键词: Olfactory bulb;    Olfactory receptor neurons;    Animal prion diseases;    Hamsters;    Neuronal dendrites;    Epithelium;    Polypeptides;    Immunofluorescence;   

DOI  :  10.1371/journal.ppat.1000837

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

This study investigated the role of prion infection of the olfactory mucosa in the shedding of prion infectivity into nasal secretions. Prion infection with the HY strain of the transmissible mink encephalopathy (TME) agent resulted in a prominent infection of the olfactory bulb and the olfactory sensory epithelium including the olfactory receptor neurons (ORNs) and vomeronasal receptor neurons (VRNs), whose axons comprise the two olfactory cranial nerves. A distinct glycoform of the disease-specific isoform of the prion protein, PrPSc, was found in the olfactory mucosa compared to the olfactory bulb, but the total amount of HY TME infectivity in the nasal turbinates was within 100-fold of the titer in the olfactory bulb. PrPSc co-localized with olfactory marker protein in the soma and dendrites of ORNs and VRNs and also with adenylyl cyclase III, which is present in the sensory cilia of ORNs that project into the lumen of the nasal airway. Nasal lavages from HY TME-infected hamsters contained prion titers as high as 103.9 median lethal doses per ml, which would be up to 500-fold more infectious in undiluted nasal fluids. These findings were confirmed using the rapid PrPSc amplification QuIC assay, indicating that nasal swabs have the potential to be used for prion diagnostics. These studies demonstrate that prion infection in the olfactory epithelium is likely due to retrograde spread from the olfactory bulb along the olfactory and vomeronasal axons to the soma, dendrites, and cilia of these peripheral neurons. Since prions can replicate to high levels in neurons, we propose that ORNs can release prion infectivity into nasal fluids. The continual turnover and replacement of mature ORNs throughout the adult lifespan may also contribute to prion shedding from the nasal passage and could play a role in transmission of natural prion diseases in domestic and free-ranging ruminants.

【 授权许可】

CC BY