NR AXAE
AU Jacobs,J.G.; Langeveld,J.P.M.; Biacabe,A.G.; Acutis,P.L.; Polak,M.P.; Gavier-Widen,D.; Buschmann,A.; Caramelli,M.; Casalone,C.; Mazza,M.; Groschup,M.H.; Erkens,J.H.F.; Davidse,A.; van Zijderveld,F.G.; Baron,T.G.M.
TI Molecular discrimination of atypical bovine spongiform encephalopathy strains from a geographical region spanning a wide area in europe
QU Journal of Clinical Microbiology 2007 Jun; 45(6): 1821-9
PT journal article; research support, non-u.s. gov't
AB Transmissible spongiform encephalopathy strains can be differentiated by their behavior in bioassays and by molecular analyses of the disease-associated prion protein (PrP) in a posttranslationally transformed conformation (PrPsc). Until recently, isolates from cases of bovine spongiform encephalopathy (BSE) appeared to be very homogeneous. However, a limited number of atypical BSE isolates have recently been identified upon analyses of the disease-associated proteinase K (PK) resistance-associated moiety of PrPsc (PrPres), suggesting the existence of at least two additional BSE PrPres variants. These are defined here as the H type and the L type, according to the higher and lower positions of the nonglycosylated PrPres band in Western blots, respectively, compared to the position of the band in classical BSE (C-type) isolates. These molecular PrPres variants, which originated from six different European countries, were investigated together. In addition to the migration properties and glycosylation profiles (glycoprofiles), the H- and L-type isolates exhibited enhanced PK sensitivities at pH 8 compared to those of the C-type isolates. Moreover, H-type BSE isolates exhibited differences in the binding of antibodies specific for N- and more C-terminal PrP regions and principally contained two aglycosylated PrPres moieties which can both be glycosylated and which is thus indicative of the existence of two PrPres populations or intermediate cleavage sites. These properties appear to be consistent within each BSE type and independent of the geographical origin, suggesting the existence of different BSE strains in cattle. The choice of three antibodies and the application of two pHs during the digestion of brain homogenates provide practical and diverse tools for the discriminative detection of these three molecular BSE types and might assist with the recognition of other variants.
IN Verglichen mit dem PrPsc klassischer BSE-Fälle (C-Typ) stellten Jacobs et al. bei PrPsc aus verschiedenen atypischen BSE-Fällen der Typen H und L bei pH 8 eine reduzierte Resistenz gegen die Proteinase K fest. Auch hinsichtlich der Bindung bestimmter Antikörper unterschieden sich die BSE-Stämme, während es innerhalb der drei BSE-Typen trotz großer geographischer Abstände keine Unterschiede gab. Demnach gibt es tatsächlich zwei unabhängige BSE-Stämme, die sehr selten und sehr weit von einander entfernt auftreten. Als Erklärung bieten sich daher wohl vor allem Spontanerkrankungen oder aufgrund von Speziesbarrieren seltene Rückübertragungen von BSE-infizierten Kleinsäugern an, die ins Futter von Rindern gelangen können. Letzteres würde allerdings eine BSE-Übertragung auf Kleinsäuger unabhängig voneinander in verschiedenen Erdteilen voraus setzen.
MH Amino Acid Sequence; Animals; Antibodies, Monoclonal/metabolism; Blotting, Western; Brain Stem/*metabolism; Cattle; Encephalopathy, Bovine Spongiform/*epidemiology/*metabolism; Endopeptidase K/metabolism/pharmacology; Europe/epidemiology; Glycosylation; Hydrogen-Ion Concentration; Molecular Sequence Data; PrPsc Proteins/*classification/*genetics/metabolism; Prions/chemistry/genetics/metabolism; *Variation (Genetics)
AD jan.langeveld@wur.nl, Department of Bacteriology and TSEs, Central Institute for Animal Disease Control (CIDC-Lelystad), 8203 AA 2004, Lelystad. The Netherlands.
SP englisch
PO USA