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Journal of Virology, June 2005, p. 7104-7112, Vol. 79, No. 11
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.11.7104-7112.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Biological and Biochemical Characteristics of Prion Strains Conserved in Persistently Infected Cell Cultures

Kazuhiko Arima,1 Noriyuki Nishida,1 Suehiro Sakaguchi,1,3 Kazuto Shigematsu,2 Ryuichiro Atarashi,1 Naohiro Yamaguchi,1 Daisuke Yoshikawa,1 Jaewoo Yoon,1 Ken Watanabe,1 Nobuyuki Kobayashi,1 Sophie Mouillet-Richard,4 Sylvain Lehmann,5 and Shigeru Katamine1*

Department of Molecular Microbiology and Immunology,1 Department of Pathology 2, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-12-4, Nagasaki 852-8523, Japan,2 PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho Kawaguchi, Saitama, Japan,3 Institut André Lwoff, CNRS UPR 1983-BP8, 94801 Villejuif Cedex, France,4 Institut de Genetique Humaine, CNRS UPR 1142, 34396 Montpellier Cedex 5, France5

Received 16 August 2004/ Accepted 18 January 2005

Abnormal prion protein (PrPSc) plays a central role in the transmission of prion diseases, but the molecular basis of prion strains with distinct biological characteristics remains to be elucidated. We analyzed the characteristics of prion disease by using mice inoculated with the Chandler and Fukuoka-1 strains propagated in a cultured mouse neuronal cell line, GT1-7, which is highly permissive to replication of the infectious agents. Strain-specific biological characteristics, including clinical manifestations, incubation period as related to the infectious unit, and pathological profiles, remained unchanged after passages in the cell cultures. We noted some differences in the biochemical aspects of PrPSc between brain tissues and GT1-7 cells which were unlikely to affect the strain phenotypes. On the other hand, the proteinase K-resistant PrP core fragments derived from Fukuoka-1-infected tissues and cells were slightly larger than those from Chandler-infected versions. Moreover, Fukuoka-1 infection, but not Chandler infection, gave an extra fragment with a low molecular weight, ~13 kDa, in both brain tissues and GT1-7 cells. This cell culture model persistently infected with different strains will provide a new insight into the understanding of the molecular basis of prion diversity.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-12-4, Nagasaki 852-8523, Japan. Phone: 81-95-849-7057. Fax: 81-95-849-7060. E-mail: katamine{at}net.nagasaki-u.ac.jp.

Journal of Virology, June 2005, p. 7104-7112, Vol. 79, No. 11
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.11.7104-7112.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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