Intraspecies Transmission of BASE Induces Clinical Dullness and Amyotrophic Changes

Abstract

The disease phenotype of bovine spongiform encephalopathy (BSE) and the molecular/ biological properties of its prion strain, including the host range and the characteristics of BSE-related disorders, have been extensively studied since its discovery in 1986. In recent years, systematic testing of the brains of cattle coming to slaughter resulted in the identification of at least two atypical forms of BSE. These emerging disorders are characterized by novel conformers of the bovine pathological prion protein (PrPTSE), named high-type (BSE-H) and low-type (BSE-L). We recently reported two Italian atypical cases with a PrPTSE type identical to BSE-L, pathologically characterized by PrP amyloid plaques and known as bovine amyloidotic spongiform encephalopathy (BASE). Several lines of evidence suggest that BASE is highly virulent and easily transmissible to a wide host range. Experimental transmission to transgenic mice overexpressing bovine PrP (Tgbov XV) suggested that BASE is caused by a prion strain distinct from the BSE isolate. In the present study, we experimentally infected Friesian and Alpine brown cattle with Italian BSE and BASE isolates via the intracerebral route. BASE-infected cattle developed amyotrophic changes accompanied by mental dullness. The molecular and neuropathological profiles, including PrP deposition pattern, closely matched those observed in the original cases. This study provides clear evidence of BASE as a distinct prion isolate and discloses a novel disease phenotype in cattle.

Properties of L-Type Bovine Spongiform Encephalopathy in Intraspecies Passages

“…Although atrophy of both type I and II muscle fibers had been detected in BASE cases in previous experiments, 8 evident changes were not detected in the skeletal muscle of the cases examined in this study. This discrepancy may have been due to the fiber-type grouping used in the previous studies, which had resulted in neurogenic atrophy of the innervated muscles, indicating that the muscular lesions in the BASE cases might not be associated with a neurogenic disorder.…”

“…5 Additional studies have demonstrated that the BSE/ JP24 isolate can be transmitted to cattle 6 and that BSE/JP 24 and BASE have nearly the same incubation period during the first passage in Holstein cattle. 6,8 Research has also suggested that during subsequent passages, the incubation period of the disease may be shorter or more stable than that of the first passage and that its characterization may vary. The primary objective of this study was to further investigate the characteristics of the second passage of the disease by clinicopathologic analysis of BSE/JP24-infected cattle.…”

“…The incubation period and molecular profiles of PrP Sc suggest that the isolate of BSE/JP24 is clearly distinct from that of C-type BSE while closely resembling that of BASE isolate. 5,6,8 Immunohistochemical analysis revealed that the patterns of PrP Sc deposition in BSE/JP24 prion-affected cattle were characterized by the presence of amyloid PrP plaques and the absence of stellate-type PrP Sc deposits. However, except for the detection of higher quantities of PrP Sc in the cerebral cortices of BSE/JP24-affected cattle, no striking differences were identified between the topographic distribution of PrP Sc in the C-type BSE and BSE/JP24 prion-affected cattle.…”

Experimental Classical Bovine Spongiform Encephalopathy

“…End point titration of the homogenate pool in RIII mice gave a titer of 10 3.5 mouse intracerebral and intraperitoneal ID 50 (median infective dose) units per gram of tissue and murine strain-type characteristics consistent with BSE-C. At 3 to 4 months of age, 30 calves were orally dosed with 100 g of the pooled brainstems, applied by syringe to the base of the tongue at the entrance to the pharynx. 35 Ten calves received no treatment and served as controls. Clinical monitoring of cattle was maintained throughout the study.…”

Examination of the Offspring of a Japanese Cow Affected with L-Type Bovine Spongiform Encephalopathy

“…Atypical BSEs are classified into 2 forms on the basis of the molecular weight of the proteinase K-resistant core fragment of the abnormal prion protein PrP Sc : L-type BSE (L-BSE) or bovine amyloidotic spongiform encephalopathy and H-type BSE (H-BSE) [3,5]. Several studies have indicated that L-BSE and H-BSE are caused by different prions with varying biological characteristics [4,11,12]. A limited number of atypical BSE cases have been reported, and sporadic occurrence may be supposed as their origin [2].…”