Longitudinal characterization of peripheral prion pathogenesis in Syrian hamsters experimentally inoculated with hamster-adapted Transmissible Mink Encephalopathy
Date
2017
Authors
Lee, Erin, author
Mathiason, Candace, advisor
Kendall, Lon, committee member
Bamburg, James, committee member
Journal Title
Journal ISSN
Volume Title
Abstract
Transmissible Spongiform Encephalopathies (TSEs) are a group of infectious, neurodegenerative diseases affecting animals, including humans. Caused by misfolded proteins called prions, TSEs are characterized by a long, asymptomatic incubation period that eventually cause neuronal death and progressive neurodegeneration. Transmissible Mink Encephalopathy (TME) is a rare TSE of mink. Syrian hamsters are susceptible to infection with TME, serving as a natural system of infection. Hyper strain (HY) of hamster-adapted TME is of particular interest due it its rapid spread into the lymphoreticular system (LRS) and blood, enabling us to study peripheral accumulation and spread of prions. Real-time quaking-induced conversion (RT-QuIC) is a rapid and sensitive assay used to detect prions, and has been used to investigate prion pathogenesis. In this study, we hypothesize that RT-QuIC can be used to detect splenic prions longitudinally throughout HY-TME infection, including during the asymptomatic phase of disease. Sixty male Syrian hamsters were extranasally (EN)-inoculated with HY-TME. We collected their spleen, blood, brain, and other tissues at early-, mid-, and late-disease course. Our study shows evidence for the temporal accumulation of prions both within the spleen and brain throughout disease. We detected RT-QuIC seeding activity in spleen and brain tissue harvested from HY-TME-inoculated hamsters in late disease, between 155 and 169 (terminal) days PI. Titers in the spleen ranged from 10-2 to 10-7. Titers in the brain ranged from 10-3 to 10-5. Additionally, we detected RT-QuIC seeding activity in the spleen of a clinical hamster before it was detectible in the brain, supporting previous work showing that the spleen is a site of peripheral prion accumulation before neuroinvasion. Our work validates the Syrian hamster, EN-inoculated with HY strain of hamster-adapted TME, as a system to evaluate peripheral prion burden within the LRS.
Description
Rights Access
Subject
detection
spleen
transmission
prion
blood
TME