H-Type Bovine Spongiform Encephalopathy: Complex Molecular Features and Similarities with Human Prion Diseases

• Published in: Prion 2007-01, Vol.1 (1), p.61-68
• Main Authors: Biacabe, Anne-Gaëlle, Jacobs, Jorg G., Bencsik, Anna, Langeveld, Jan P.M., Baron, Thierry G.M.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies - chemistry; Antibodies - immunology; Antibody Specificity; Binding; Biology; Bioscience; Blotting, Western; Calcium; Cancer; Cattle; Cell; Cycle; Encephalopathy, Bovine Spongiform - immunology; Encephalopathy, Bovine Spongiform - metabolism; Encephalopathy, Bovine Spongiform - transmission; Female; Humans; Landes; Mice; Organogenesis; Protein Structure, Tertiary; Proteins; PrPSc Proteins - analysis; PrPSc Proteins - immunology; PrPSc Proteins - metabolism; Research Paper
• ISSN: 1933-6896; 1933-690X
• DOI: 10.4161/pri.1.1.3828

We previously reported that some cattle affected by bovine spongiform encephalopathy (BSE) showed distinct molecular features of the protease-resistant pion protein (PrPres ) in Western blot, with a 1-2 kDa higher apparent molecular mass of the unglycosylated PrPres associated with labelling by antibodies against the 86-107 region of the bovine PrP protein (H-type BSE). By Western blot analyses of PrPres, we now showed that the essential features initially described in cattle were observed with a panel of different antibodies and were maintained after transmission of the disease in C57Bl/6 mice. In addition, antibodies against the C-terminal region of PrP revealed a second, more C-terminally cleaved, form of PrPres (PrPres #2), which, in unglycosylated form, migrated as a ≈ 14 kDa fragment. Furthermore, a PrPres fragment of ≈ 7kDa, which was not labelled by C-terminus-specific antibodies and was thus presumed to be a product of cleavage at both N- and C-terminal sides of PrP protein, was also detected. Both PrPres #2 and ≈ 7 kDa PrPres were detected in cattle and in C57Bl/6 infected mice. These complex molecular features are reminiscent of findings reported in human prion diseases. This raises questions regarding the respective origins and pathogenic mechanisms in prion diseases of animals and humans.