Patterns of PrPCWD accumulation during the course of chronic wasting disease infection in orally inoculated mule deer (Odocoileus hemionus)

Abstract

Patterns of abnormal prion protein (PrP) accumulation during the course of chronic wasting disease (CWD) infection were studied and the distribution and timing of disease-associated PrP (PrP(CWD)) deposition and lesions in 19 mule deer (Odocoileus hemionus) 90-785 days after oral inoculation were described. PrP(CWD) deposition occurred relatively rapidly and widely in lymphoid tissues, later in central and peripheral nervous tissues and sporadically in a variety of tissues and organs in terminal disease stages. Development of spongiform encephalopathy lagged behind PrP(CWD) deposition in the central nervous system (CNS), but occurred in the same neuroanatomical locations. PrP(CWD) deposition in the lymphatic and nervous systems tended to be consistent and progressive in specific organs and tissues. Locations of PrP(CWD) deposition were similar between deer of two PrP genotypes (225SS and 225SF), but the time course differed between genotypes: in 225SF deer, PrP(CWD) accumulated more slowly in lymphatic tissues than in 225SS animals, but that disparity was small in comparison to the disparity between genotypes in timing of deposition in CNS tissue. These data confirm retropharyngeal lymph node and medulla oblongata at the level of the obex as early sites of PrP(CWD) accumulation in mule deer with CWD. Data on the relative time frames for and genetic influences on PrP(CWD) accumulation may also offer insights about epidemic dynamics and potential control strategies.