Chronic wasting disease (CWD) susceptibility of several North American rodents that are sympatric with cervid CWD epidemics

Abstract

Chronic wasting disease (CWD) is a highly contagious always fatal neurodegenerative disease that is currently known to naturally infect only species of the deer family, Cervidae. CWD epidemics are occurring in free-ranging cervids at several locations in North America, and other wildlife species are certainly being exposed to infectious material. To assess the potential for transmission, we intracerebrally inoculated four species of epidemic-sympatric rodents with CWD. Transmission was efficient in all species; the onset of disease was faster in the two vole species than the two Peromyscus spp. The results for inocula prepared from CWD-positive deer with or without CWD-resistant genotypes were similar. Survival times were substantially shortened upon second passage, demonstrating adaptation. Unlike all other known prion protein sequences for cricetid rodents that possess asparagine at position 170, our red-backed voles expressed serine and refute previous suggestions that a serine in this position substantially reduces susceptibility to CWD. Given the scavenging habits of these rodent species, the apparent persistence of CWD prions in the environment, and the inevitable exposure of these rodents to CWD prions, our intracerebral challenge results indicate that further investigation of the possibility of natural transmission is warranted.

FIG. 1.

Overlap of rodent distributions and CWD epidemics. Black dots show known locations of CWD in free-ranging cervids, and the green is the rodent's distribution. (A) Meadow voles; (B) red-backed voles; (C) white-footed mice; (D) deer mice.

FIG. 2.

Survival curves for CWD-challenged meadow voles (black; n = 18), red-backed voles (red; n = 10), deer mice (blue; n = 20), and white-footed mice (green; n = 17). Of 53 endpoint animals tested for PrP^d by either immunoblotting or IHC, only 4 had undetectable levels: 1 red-backed vole and 3 white-footed mice. The genotypes of the four deer used for the inocula did not appear to have any effect on the incubation distribution (square = GG, circle = GS; an asterisk [*] means the observation was censored).

FIG. 3.

Immunoblots of four of the white-tailed deer inocula used for challenges. Each inoculum used obex tissue from only a single deer. Each inoculum is shown without (−PK) and with (+PK) PK digestion. The two inocula on the left are from deer with the GG PrP genotype, and the two on the right are from deer with the GS (resistant) genotype. No consistent differences are obvious.

FIG. 4.

Representative immunoblots for white-footed mice (Pl), deer mice (Pm), red-backed voles (Mg), and meadow voles (Mp). The two left-most lanes are for a meadow vole that was challenged with inoculum prepared from CWD-negative deer brain tissue. The right control lane was digested with PK (+PK), and the left control lane was not (−PK). The other eight lanes are for animals that received inoculum from CWD-positive deer; these lanes were PK digested, and all show the presence of PK-resistant PrP^d. Within each species, the left column labeled GS is for a subject that received inoculum from a CWD-positive deer with the GS genotype; the right column is a subject that received the GG genotype.

FIG. 5.

Glycoform proportions for a sample of first-passage (A) and second-passage (B) subjects. Symbols: red square, deer used for inoculum; black circle, meadow vole; blue star, red-backed vole; green plus, white-footed mouse; purple diamond, deer mouse. The solid black dot is for reference; it is the centroid for the monoglycosylated dominated phenotype of mouse-adapted 139A scrapie expressed in murid hosts (from Fig. 2 of Agrimi et al. [1]).

FIG. 6.

PrP^d deposition in the thalamus. (A) Meadow voles; (B) red-backed voles; (C) white-footed mice; (D) deer mice. The scale is 10 μm.