Oral transmission and early lymphoid tropism of chronic wasting disease PrPres in mule deer fawns (Odocoileus hemionus)

Mule deer fawns (Odocoileus hemionus) were inoculated orally with a brain h omogenate prepared from mule deer with naturally occurring chronic wasting disease (CWD), a prion-induced transmissible spongiform encephalopathy. Faw ns were necropsied and examined for PrPres, the abnormal prion protein isof orm, at 10, 42, 53, 77, 78 and 80 days post-inoculation (p.i.) using an imm unohistochemistry assay modified to enhance sensitivity. PrPres was detecte d in alimentary-tract-associated lymphoid tissues (one or more of the follo wing: retropharyngeal lymph node, tonsil, Peyer's patch and ileocaecal lymp h node) as early as 42 days p.i. and in all fawns examined thereafter (53 t o 80 days p.i.). No PrPres staining was detected in lymphoid tissue of thre e control fawns receiving a control brain inoculum, nor was PrPres detectab le in neural tissue of any fawn. PrPres-specific staining was markedly enha nced by sequential tissue treatment with formic acid, proteinase K and hydr ated autoclaving prior to immunohistochemical staining with monoclonal anti body F89/160.1.5. These results indicate that CWD PrPres can be detected in lymphoid tissues draining the alimentary tract within a few weeks after or al exposure to infectious prions and may reflect the initial pathway of CWD infection in deer. The rapid infection of deer fawns following exposure by the most plausible natural route is consistent with the efficient horizont al transmission of CWD in nature and enables accelerated studies of transmi ssion and pathogenesis in the native species.