L-Type Bovine Spongiform Encephalopathy in Genetically Susceptible and Resistant Sheep: Changes in Prion Strain or Phenotypic Plasticity of the Disease-Associated Prion Protein?

• Published in: The Journal of infectious diseases Vol. 209; no. 6; pp. 950 - 959
• Main Authors: Nicot, Simon, Bencsik, Anna, Migliore, Sergio, Canal, Dominique, Leboidre, Mikael, Agrimi, Umberto, Nonno, Romolo, Baron, Thierry
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.03.2014
• Subjects: Animal models; Animals; Antibodies; Biological and medical sciences; Brain Chemistry; Cattle; Creutzfeldt Jakob syndrome; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease models; Encephalopathy, Bovine Spongiform - classification; Encephalopathy, Bovine Spongiform - genetics; Encephalopathy, Bovine Spongiform - metabolism; Encephalopathy, Bovine Spongiform - pathology; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Infectious diseases; Medical sciences; Mice; Mice, Transgenic; Microbiology; Neurology; Non conventional transmissible agents; Phenotype; Prion diseases; Prions; Prions - chemistry; Prions - genetics; Prions - metabolism; Sheep; Spleen; Transgenic animals; Ungulates; Prion disease; Nervous system diseases; Farming animal; Phenotypic plasticity; Bovine spongiform encephalopathy; Cerebral disorder; Strain; Infection; Resistance; Vertebrata; Mammalia; Central nervous system disease; Sheep; Degenerative disease; Prion; Artiodactyla; Veterinary; Ungulata; strain; BSE; CH1641; L-BSE; prion; scrapie; BASE
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jit596

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 proteaseresistant 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 CHI641. 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 CHI641 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.