Atypical BSE (BASE) transmitted from asymptomatic aging cattle to a primate

Area of Science:

• Neuroscience
• Prion Diseases
• Veterinary Medicine

Background:

• Human variant Creutzfeldt-Jakob Disease (vCJD) is linked to classical Bovine Spongiform Encephalopathy (cBSE) from cattle.
• Atypical BSE (BASE) strains identified in cattle raise concerns about human susceptibility.

Purpose of the Study:

• To investigate the pathogenicity of atypical BASE in a primate model.
• To compare BASE with cBSE and vCJD in non-human primates.
• To explore potential links between atypical prion strains and human CJD.

Main Methods:

• Inoculation of brain homogenates from cBSE and BASE-infected cattle into cynomolgus monkeys.
• Comparison of clinical signs, histopathology, and prion protein (PrPres) biochemistry.
• Analysis of PrPres biochemical signature in inoculated primates and human sporadic CJD patients.

Main Results:

• BASE infection in a monkey resulted in shorter survival and distinct clinical/histopathological outcomes compared to cBSE.
• The BASE-infected primate exhibited a unique PrPres biochemical signature with higher proteinase K sensitivity.
• This signature was also identified in a subset of human sporadic CJD patients (MM type 2 PrP genotype).

Conclusions:

• Atypical BASE may exhibit higher pathogenicity in primates than classical BSE.
• A potential link exists between atypical prion strains and a specific group of sporadic CJD cases.
• Continued vigilance and public health measures are crucial due to the emergence of atypical BSE strains.