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Journal of Virology, April 2009, p. 3852-3860, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.01740-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Region Approximately between Amino Acids 81 and 137 of Proteinase K-Resistant PrPSc Is Critical for the Infectivity of the Chandler Prion Strain {triangledown}

Ryo Shindoh, Chan-Lan Kim,{dagger} Chang-Hyun Song, Rie Hasebe, and Motohiro Horiuchi*

Laboratory of Prion Diseases, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan

Received 17 August 2008/ Accepted 16 January 2009

Although the major component of the prion is believed to be the oligomer of PrPSc, little information is available concerning regions on the PrPSc molecule that affect prion infectivity. During the analysis of PrPSc molecules from various prion strains, we found that PrPSc of the Chandler strain showed a unique property in the conformational-stability assay, and this property appeared to be useful for studying the relationship between regions of the PrPSc molecule and prion infectivity. Thus, we analyzed PrPSc of the Chandler strain in detail and analyzed the infectivities of the N-terminally denatured and truncated forms of proteinase K-resistant PrP. The N-terminal region of PrPSc of the Chandler strain showed region-dependent resistance to guanidine hydrochloride (GdnHCl) treatment. The region approximately between amino acids (aa) 81 and 137 began to be denatured by treatment with 1.5 M GdnHCl. Within this stretch, the region comprising approximately aa 81 to 90 was denatured almost completely by 2 M GdnHCl. Furthermore, the region approximately between aa 90 and 137 was denatured completely by 3 M GdnHCl. However, the C-terminal region thereafter was extremely resistant to the GdnHCl treatment. This property was not observed in PrPSc molecules of other prion strains. Denaturation of the region between aa 81 and 137 by 3 M GdnHCl significantly prolonged the incubation periods in mice compared to that for the untreated control. More strikingly, the denaturation and removal of this region nearly abolished the infectivity. This finding suggests that the conformation of the region between aa 81 and 137 of the Chandler strain PrPSc molecule is directly associated with prion infectivity.

* Corresponding author. Present address: Laboratory of Prion Diseases, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan. Phone and fax: 81-11-706-5293. E-mail: horiuchi{at}vetmed.hokudai.ac.jp

{triangledown} Published ahead of print on 28 January 2009.

{dagger} Present address: Foreign Animal Disease Division, Animal Disease Control Department, National Veterinary Research and Quarantine Service, 480 Anyang-6 dong, Manan-gu, Anyang 430-824, Republic of Korea.

Journal of Virology, April 2009, p. 3852-3860, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.01740-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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