L-type bovine spongiform encephalopathy in genetically susceptible and resistant sheep: changes in prion strain or phenotypic plasticity of the disease-associated prion protein?
BACKGROUND
Sheep with prion protein (PrP) gene polymorphisms QQ171 and RQ171 were shown to be susceptible to the prion causing L-type bovine spongiform encephalopathy (L-BSE), although RQ171 sheep specifically propagated a distinctive prion molecular phenotype in their brains, characterized by a high molecular mass protease-resistant PrP fragment (HMM PrPres), distinct from L-BSE in QQ171 sheep.


METHODS
The resulting infectious and biological properties of QQ171 and RQ171 ovine L-BSE prions were investigated in transgenic mice expressing either bovine or ovine PrP.


RESULTS
In both mouse lines, ovine L-BSE transmitted similarly to cattle-derived L-BSE, with respect to survival periods, histopathology, and biochemical features of PrPres in the brain, as well as splenotropism, clearly differing from ovine classic BSE or from scrapie strain CH1641. Nevertheless and unexpectedly, HMM PrPres was found in the spleen of ovine PrP transgenic mice infected with L-BSE from RQ171 sheep at first passage, reminiscent, in lymphoid tissues only, of the distinct PrPres features found in RQ171 sheep brains.


CONCLUSIONS
The L-BSE agent differs from both ovine classic BSE or CH1641 scrapie maintaining its specific strain properties after passage in sheep, although striking PrPres molecular changes could be found in RQ171 sheep and in the spleen of ovine PrP transgenic mice.
Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail, Unité Maladies Neuro-Dégénératives, Lyon, France.
Simon
S
Nicot
Anna
A
Bencsik
Sergio
S
Migliore
Dominique
D
Canal
Mikael
M
Leboidre
Umberto
U
Agrimi
Romolo
R
Nonno
Thierry
T
Baron
D000818:Animals; D001923:Brain Chemistry; D002417:Cattle; D016643:Encephalopathy, Bovine Spongiform / Q000145:classification* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020022:Genetic Predisposition to Disease; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D011328:Prions / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012756:Sheep
D011328:Prions
BASE; BSE; CH1641; L-BSE; prion; scrapie; strain