Experimental interspecies transmission studies of the transmissible spongiform encephalopathies to cattle

Abstract

Abstract. Prion diseases or transmissible spongiform encephalopathies (TSEs) of animals include scrapie of sheep and goats; transmissible mink encephalopathy (TME); chronic wasting disease (CWD) of deer, elk and moose; and bovine spongiform encephalopathy (BSE) of cattle. The emergence of BSE and its spread to human beings in the form of variant Creutzfeldt-Jakob disease (vCJD) resulted in interest in susceptibility of cattle to CWD, TME and scrapie. Experimental cross-species transmission of TSE agents provides valuable information for potential host ranges of known TSEs. Some interspecies transmission studies have been conducted by inoculating disease-causing prions intracerebrally (IC) rather than orally; the latter is generally effective in intraspecies transmission studies and is considered a natural route by which animals acquire TSEs. The "species barrier" concept for TSEs resulted from unsuccessful interspecies oral transmission attempts. Oral inoculation of prions mimics the natural disease pathogenesis route whereas IC inoculation is rather artificial; however, it is very efficient since it requires smaller dosage of inoculum, and typically results in higher attack rates and reduces incubation time compared to oral transmission. A species resistant to a TSE by IC inoculation would have negligible potential for successful oral transmission. To date, results indicate that cattle are susceptible to IC inoculation of scrapie, TME, and CWD but it is only when inoculated with TME do they develop spongiform lesions or clinical disease similar to BSE. Importantly, cattle are resistant to oral transmission of scrapie or CWD; susceptibility of cattle to oral transmission of TME is not yet determined.

Changes in Retinal Function and Morphology Are Early Clinical Signs of Disease in Cattle with Bovine Spongiform Encephalopathy

“…The retina is the most accessible part of the CNS and is amenable to non-invasive assessment of morphology and function. We have previously demonstrated that functional changes develop in the retina of cattle inoculated with transmissible mink encephalopathy, a TSE with microscopic features similar to those of BSE [28], months prior to other clinical signs of disease [24]. Here we describe changes in retinal morphology and function over time in animals inoculated with two different strains of BSE; classical foodborne BSE, which transmits to humans as vCJD [6,29,30], and atypical high-type BSE (BSE-H) diagnosed in the US in 2004 [31].…”

Chronic wasting disease of cervids

“…Cattle failed to develop SE although PrP res was detected in the CNS (Hamir et al, 2011). In sheep, only two of eight became infected: one (ARQ/VRQ at codons 136, 154, and 171) developing clinical signs, SE lesions and was PrP res positive at 35 months post inoculation (mpi) and one (ARQ/ARQ) SE and PrP res positive but no clinical signs at 72 months pi; two ARQ/ARQ and four ARQ/ARR were negative for PrP res at 36-72 mpi (Hamir et al, 2006b).…”

“…In sheep, only two of eight became infected: one (ARQ/VRQ at codons 136, 154, and 171) developing clinical signs, SE lesions and was PrP res positive at 35 months post inoculation (mpi) and one (ARQ/ARQ) SE and PrP res positive but no clinical signs at 72 months pi; two ARQ/ARQ and four ARQ/ARR were negative for PrP res at 36-72 mpi (Hamir et al, 2006b). Oral transmission into cattle failed (to nine years post infection) (Hamir et al, 2011).…”

“…It has been possible to infect domestic cattle, goats and sheep by IC inoculation, although not in all individuals and with several-year incubation periods in cattle and goats (Hamir et al, 2006b(Hamir et al, , 2011. Cattle failed to develop SE although PrP res was detected in the CNS (Hamir et al, 2011).…”

Safety, specificity and immunogenicity of a PrPSc-specific prion vaccine based on the YYR disease specific epitope

“…25 Cattle orally inoculated with CWD-infected brains, or housed with CWD-positive deer, do not contract a TSE but cattle inoculated intracerebrally with CWD do develop a prion disease. 18,26 This highlights the potential, given the correct circumstances, for CWD to overcome this species barrier. Prion disease transmission from cervids to cattle could also occur through any number of intermediate species.…”