Scrapie is a naturally occurring spongiform encephalopathy of sheep and goats which causes clinical and pathological changes similar to those of Creutzfeld-Jakob and Kuru diseases of man. A unique protein called prion protein (PrP) has been found to be a major component of purified samples of scrapie infectivity and is believed by some people to be the actual infectious agent. We previously isolated two cDNA clones of the PrP mRNA from scrapie-infected mouse brain. We have ligated the cloned mouse PrP cDNA into an expression plasmid containing bovine papilloma virus (BPV) and have induced PrP synthesis in mouse epithelial cells. To test the possible infectivity of these expressed proteins, sonicated cell suspensions were inoculated intracerebrally into weanling RML mice. By 160 days post-inoculation no mice had developed clinical signs of scrapie suggesting that PrP may not be the infectious scrapie agent, but is more likely to be a normal cellular protein which accumulates in aggregated forms as a result of the disease process. The possibility that post- translational modification of the endogenous gene product results in creation of the infectious scrapie agent has not been completely excluded. Because animal tissues have not provided satisfactory substrates for the biochemical analysis or isolation of the scrapie agent, we have continued to work on development of scrapie infected tissue culture systems. Toward this goal neuroblastoma cell lines of mouse origin were successfully infected with scrapie agent. Infected cultures were maintained through 21 passages, well beyond the number needed to assure that replication had occurred. Infection appeared to be species-specific in that agent derived from hamster brain did not infect the mouse derived neuroblastoma cell lines. Positive clones have now been derived from these original cultures. They contain approximately 50-100 fold more agent than was found in the original cultures and should provide a new, more homogenous source of scrapie agent.
| Race, Brent L; Meade-White, Kimberly D; Ward, Anne et al. (2007) Levels of abnormal prion protein in deer and elk with chronic wasting disease. Emerg Infect Dis 13:824-30 |
| Meade-White, Kimberly; Race, Brent; Trifilo, Matthew et al. (2007) Resistance to chronic wasting disease in transgenic mice expressing a naturally occurring allelic variant of deer prion protein. J Virol 81:4533-9 |
| Raymond, Gregory J; Raymond, Lynne D; Meade-White, Kimberly D et al. (2007) Transmission and adaptation of chronic wasting disease to hamsters and transgenic mice: evidence for strains. J Virol 81:4305-14 |
| Kocisko, David A; Caughey, Byron; Morrey, John D et al. (2006) Enhanced antiscrapie effect using combination drug treatment. Antimicrob Agents Chemother 50:3447-9 |
| Kocisko, David A; Vaillant, Andrew; Lee, Kil Sun et al. (2006) Potent antiscrapie activities of degenerate phosphorothioate oligonucleotides. Antimicrob Agents Chemother 50:1034-44 |
| Kocisko, David A; Caughey, Winslow S; Race, Richard E et al. (2006) A porphyrin increases survival time of mice after intracerebral prion infection. Antimicrob Agents Chemother 50:759-61 |
| Criado, Jose R; Sanchez-Alavez, Manuel; Conti, Bruno et al. (2005) Mice devoid of prion protein have cognitive deficits that are rescued by reconstitution of PrP in neurons. Neurobiol Dis 19:255-65 |
| Chesebro, Bruce; Trifilo, Matthew; Race, Richard et al. (2005) Anchorless prion protein results in infectious amyloid disease without clinical scrapie. Science 308:1435-9 |
| Silveira, Jay R; Raymond, Gregory J; Hughson, Andrew G et al. (2005) The most infectious prion protein particles. Nature 437:257-61 |
| Kocisko, David A; Morrey, John D; Race, Richard E et al. (2004) Evaluation of new cell culture inhibitors of protease-resistant prion protein against scrapie infection in mice. J Gen Virol 85:2479-83 |
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