Progression of chronic wasting disease in white-tailed deer analyzed by serial biopsy RT-QuIC and immunohistochemistry.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Immunohistochemistry*; Nucleic Acid Amplification Techniques/*methods ; Wasting Disease, Chronic/*pathology; Administration, Oral ; Animals ; Deer ; Disease Progression ; Longitudinal Studies ; Lymphoid Tissue/metabolism ; Lymphoid Tissue/pathology ; Palatine Tonsil/metabolism ; Palatine Tonsil/pathology ; Prion Proteins/genetics ; Prion Proteins/metabolism ; Prions/administration & dosage ; Wasting Disease, Chronic/metabolism

Chronic wasting disease (CWD) continues to spread or be recognized in the United States, Canada, and Europe. CWD is diagnosed by demonstration of the causative misfolded prion protein (PrPCWD) in either brain or lymphoid tissue using immunodetection methods, with immunohistochemistry (IHC) recognized as the gold standard. In recent years, in vitro amplification assays have been developed that can detect CWD prion seeding activity in tissues, excreta, and body fluids of affected cervids. These methods potentially offer earlier and more facile detection of CWD, both pre- and post-mortem. Here we provide a longitudinal profile of CWD infection progression, as assessed by both real-time quaking-induced conversion (RT-QuIC) and IHC on serial biopsies of mucosal lymphoid tissues of white-tailed deer orally exposed to low doses of CWD prions. We report that detection of CWD infection by RT-QuIC preceded that by IHC in both tonsil and recto-anal lymphoid tissue (RAMALT) in 14 of 19 deer (74%). Of the 322 biopsy samples collected in post-exposure longitudinal monitoring, positive RT-QuIC results were obtained for 146 samples, 91 of which (62%) were concurrently also IHC-positive. The lower frequency of IHC positivity was manifest most in the earlier post-exposure periods and in biopsies in which lymphoid follicles were not detected. For all deer in which RT-QuIC seeding activity was detected in a tonsil or RAMALT biopsy, PrPCWD was subsequently or concurrently detected by IHC. Overall, this study (a) provides a longitudinal profile of CWD infection in deer after low yet infectious oral prion exposure; (b) illustrates the value of RT-QuIC for sensitive detection of CWD; and (c) demonstrates an ultimate high degree of correlation between RT-QuIC and IHC positivity as CWD infection progresses.
Competing Interests: The authors have declared that no competing interests exist.

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P01 AI077774 United States AI NIAID NIH HHS; R01 AI112956 United States AI NIAID NIH HHS; R01 NS061902 United States NS NINDS NIH HHS

0 (Prion Proteins)
0 (Prions)

Date Created: 20200215 Date Completed: 20200424 Latest Revision: 20201213

20221213

PMC7021286

10.1371/journal.pone.0228327

32059005