Distinct molecular phenotypes in bovine prion diseases

Bovine spongiform encephalopathy (BSE) in cattle, the most likely cause of variant Creutzfeldt–Jakob disease in humans, is thought to be caused by a unique infectious agent, with stable features, even when transmitted to other species. Here, we show the existence of an atypical molecular phenotype among cattle diagnosed with BSE in France. Following western blot analysis, three cases showed unusual features of the electrophoretic profiles of the protease‐resistant prion protein (PrPres) accumulating in the brain. The PrPres patterns were similar in these three atypical cases, showing a higher molecular mass of unglycosylated PrPres and strong labelling by P4 monoclonal antibody compared to 55 typical BSE cases. This finding suggests either some phenotypic modifications of PrPres following infection by the BSE agent or the existence of alternative origins of such diseases in cattle.

[1]  Andrew F. Hill,et al.  The same prion strain causes vCJD and BSE , 1997, Nature.

[2]  J. Collinge,et al.  BSE prions propagate as either variant CJD‐like or sporadic CJD‐like prion strains in transgenic mice expressing human prion protein , 2002, The EMBO journal.

[3]  H. Budka,et al.  Molecular classification of sporadic Creutzfeldt-Jakob disease. , 2003, Brain : a journal of neurology.

[4]  T. Baron.  Identification of Inter‐Species Transmission of Prion Strains , 2002, Journal of neuropathology and experimental neurology.

[5]  M. Groschup,et al.  Immunological characterization of the sheep prion protein expressed as fusion proteins in Escherichia coli. , 1999, FEMS immunology and medical microbiology.

[6]  S. Prusiner,et al.  Compelling transgenetic evidence for transmission of bovine spongiform encephalopathy prions to humans. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[7]  D. Calavas,et al.  Sensitivity of the Western blot detection of prion protein PrPres in natural sheep scrapie. , 1998, Journal of virological methods.

[8]  Andrew F. Hill,et al.  Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD , 1996, Nature.

[9]  M. Groschup,et al.  Synthetic peptide vaccines yield monoclonal antibodies to cellular and pathological prion proteins of ruminants. , 1998, The Journal of general virology.

[10]  D. Calavas,et al.  Similar Signature of the Prion Protein in Natural Sheep Scrapie and Bovine Spongiform Encephalopathy-Linked Diseases , 1999, Journal of Clinical Microbiology.

[11]  S. Cousens,et al.  Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent , 1997, Nature.

[12]  N. Hunter,et al.  Molecular analysis of ovine prion protein identifies similarities between BSE and an experimental isolate of natural scrapie, CH1641. , 1999, The Journal of general virology.

[13]  A. Bencsik,et al.  Targeted surveillance to assess the prevalence of BSE in high-risk populations in western France and the associated risk factors , 2002, Veterinary Record.

[14]  M. Stack,et al.  Differentiation of prion protein glycoforms from naturally occurring sheep scrapie, sheep-passaged scrapie strains (CH1641 and SSBP1), bovine spongiform encephalopathy (BSE) cases and Romney and Cheviot breed sheep experimentally inoculated with BSE using two monoclonal antibodies , 2002, Acta Neuropathologica.

[15]  N. Hunter,et al.  Different forms of the bovine PrP gene have five or six copies of a short, G-C-rich element within the protein-coding exon. , 1991, The Journal of general virology.

[16]  G. Macchi,et al.  Prion protein glycotype analysis in familial and sporadic Creutzfeldt-Jakob disease patients , 1999, Brain Research Bulletin.

[17]  D. Calavas,et al.  Efficiency of Western blotting for the specific immunodetection of proteinase K-resistant prion protein in BSE diagnosis in France , 2000, Veterinary Record.

[18]  D. Calavas,et al.  Comparison of French natural scrapie isolates with bovine spongiform encephalopathy and experimental scrapie infected sheep , 2000, Neuroscience Letters.

[19]  T. Baron,et al.  Molecular Analysis of the Abnormal Prion Protein during Coinfection of Mice by Bovine Spongiform Encephalopathy and a Scrapie Agent , 2001, Journal of Virology.

[20]  M. Bruce.  Strain Typing Studies of Scrapie and BSE , 1996 .

[21]  J. Collinge,et al.  Molecular screening of sheep for bovine spongiform encephalopathy , 1998, Neuroscience Letters.

[22]  J. Collinge,et al.  Strain-specific prion-protein conformation determined by metal ions , 1999, Nature Cell Biology.

[23]  M. Groschup,et al.  Differences in Proteinase K Resistance and Neuronal Deposition of Abnormal Prion Proteins Characterize Bovine Spongiform Encephalopathy (BSE) and Scrapie Strains , 1999, Molecular medicine.