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Journal of Virology, January 2005, p. 934-943, Vol. 79, No. 2
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.2.934-943.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Biochemical Fingerprints of Prion Infection: Accumulations of Aberrant Full-Length and N-Terminally Truncated PrP Species Are Common Features in Mouse Prion Disease

Tao Pan,1 Poki Wong,1 Binggong Chang,1 Chaoyang Li,1 Ruliang Li,1 Shin-Chung Kang,1 Thomas Wisniewski,2 and Man-Sun Sy1,3*

Institute of Pathology,1 Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio,3 Department of Neurology, Psychiatry and Pathology, New York University School of Medicine, New York, New York2

Received 22 March 2004/ Accepted 24 August 2004

Infection with any one of three strains of mouse scrapie prion (PrPSc), 139A, ME7, or 22L, results in the accumulation of two underglycosylated, full-length PrP species and an N-terminally truncated PrP species that are not detectable in uninfected animals. The levels of the N-terminally truncated PrP species vary depending on PrPSc strain. Furthermore, 22L-infected brains consistently have the highest levels of proteinase K (PK)-resistant PrP species, followed by ME7- and 139A-infected brains. The three strains of PrPSc are equally susceptible to PK and proteases papain and chymotrypsin. Their protease resistance patterns are also similar. In sucrose gradient velocity sedimentation, the aberrant PrP species partition with PrPSc aggregates, indicating that they are physically associated with PrPSc. In ME7-infected animals, one of the underglycosylated, full-length PrP species is detected much earlier than the other, before both the onset of clinical disease and the detection of PK-resistant PrP species. In contrast, the appearance of the N-terminally truncated PrP species coincides with the presence of PK-resistant species and the manifestation of clinical symptoms. Therefore, accumulation of the underglycosylated, full-length PrP species is an early biochemical fingerprint of PrPSc infection. Accumulation of the underglycosylated, full-length PrP species and the aberrant N-terminally truncated PrP species may be important in the pathogenesis of prion disease.

* Corresponding author. Mailing address: Room 933, BRB, School of Medicine, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44107-1712. Phone: (216) 368-1290. Fax: (216) 368-1357. E-mail: mxs92{at}po.cwru.edu.

Journal of Virology, January 2005, p. 934-943, Vol. 79, No. 2
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.2.934-943.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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