Very low oral exposure to prions of brain or saliva origin can transmit chronic wasting disease

Abstract

The minimum infectious dose required to induce CWD infection in cervids remains unknown, as does whether peripherally shed prions and/or multiple low dose exposures are important factors in CWD transmission. With the goal of better understand CWD infection in nature, we studied oral exposures of deer to very low doses of CWD prions and also examined whether the frequency of exposure or prion source may influence infection and pathogenesis. We orally inoculated white-tailed deer with either single or multiple divided doses of prions of brain or saliva origin and monitored infection by serial longitudinal tissue biopsies spanning over two years. We report that oral exposure to as little as 300 nanograms (ng) of CWD-positive brain or to saliva containing seeding activity equivalent to 300 ng of CWD-positive brain, were sufficient to transmit CWD disease. This was true whether the inoculum was administered as a single bolus or divided as three weekly 100 ng exposures. However, when the 300 ng total dose was apportioned as 10, 30 ng doses delivered over 12 weeks, no infection occurred. While low-dose exposures to prions of brain or saliva origin prolonged the time from inoculation to first detection of infection, once infection was established, we observed no differences in disease pathogenesis. These studies suggest that the CWD minimum infectious dose approximates 100 to 300 ng CWD-positive brain (or saliva equivalent), and that CWD infection appears to conform more with a threshold than a cumulative dose dynamic.

Review on PRNP genetics and susceptibility to chronic wasting disease of Cervidae

“…CWD is characterized by an extensive deposition of PrP Sc (termed here PrP CWD ) and of infectivity in the CNS and in the lymphoid tissue. In addition PrP CWD and infectivity can be discarded in bodily fluids (urine, faeces, saliva), placenta, decomposing carcasses from dead animals and fomites from the suites of infectious deer prions [3][4][5]. Edible tissues in which PrP CWD has been detected are heart, liver, kidney, tongue, pancreas, blood, adipose tissue, lymphoreticular system and antler velvet [6][7][8][9][10][11].…”

Chronic wasting disease: a cervid prion infection looming to spillover

“…Similarly in elk, differences in incubation period were observed to range between 1.8 to 5.2 years depending on the elk PRNP genotype [ 34 – 36 ]. During the asymptomatic period, both captive and wild infected cervids contribute to the spread of CWD as they accumulate considerable amounts of prion infectivity throughout the body, which is shed through secretions and excretions into the environment [ 6 , 37 , 38 ].…”

“…Secretions (saliva) and excretions (urine and feces) of CWD-infected cervids contain considerable CWD infectivity. The minimum infectious dose in saliva required for a deer to become infected, assuming a single oral exposure to CWD prions, is equivalent to the infectivity contained in 100–300 ng of brain (approximate equivalent of 30 mL of CWD-positive saliva) [ 6 ]. Secretions and excretions from CWD positive animals and the decomposition of diseased carcasses contaminate the environment, in which prions can persist in a bioavailable state for years [ 38 , 64 – 66 ].…”

“…In addition to CWD, prion diseases include scrapie in sheep and goats, bovine spongiform encephalopathy (BSE), transmissible mink encephalopathy (TME), and Creutzfeldt-Jakob disease (CJD) in humans. CWD is the only prion disease affecting both wild and farmed animals and stands out for being highly contagious, widespread and persistent in the environment, which facilitates the transmission of the disease and hinders its control in deer populations [ 3 – 6 ].…”

Prion protein polymorphisms in Michigan white-tailed deer (Odocoileus virginianus)

“…Two non-synonymous polymorphisms within the prion gene ( PRNP ) resulting in changes to amino acids 95 (Q95H) and 96 (G96S), have been most commonly found to be associated with reduced disease susceptibility in white-tailed deer [ 22–35 ]. While neither have been shown to provide complete protection from CWD infection, they have been linked to reductions in genotype-specific prevalence rates [ 26 , 29–31 , 36 ] or increased duration of incubation [ 37 ].…”