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Journal of Virology, August 1999, p. 6245-6250, Vol. 73, No. 8
0022-538X/99/$04.00+0

Species-Independent Inhibition of Abnormal Prion Protein (PrP) Formation by a Peptide Containing a Conserved PrP Sequence

Joëlle Chabry,dagger Suzette A. Priola, Kathy Wehrly, Jane Nishio, James Hope,Dagger and Bruce Chesebro*

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840

Received 7 January 1999/Accepted 21 April 1999

Conversion of the normal protease-sensitive prion protein (PrP) to its abnormal protease-resistant isoform (PrP-res) is a major feature of the pathogenesis associated with transmissible spongiform encephalopathy (TSE) diseases. In previous experiments, PrP conversion was inhibited by a peptide composed of hamster PrP residues 109 to 141, suggesting that this region of the PrP molecule plays a crucial role in the conversion process. In this study, we used PrP-res derived from animals infected with two different mouse scrapie strains and one hamster scrapie strain to investigate the species specificity of these conversion reactions. Conversion of PrP was found to be completely species specific; however, despite having three amino acid differences, peptides corresponding to the hamster and mouse PrP sequences from residues 109 to 141 inhibited both the mouse and hamster PrP conversion systems equally. Furthermore, a peptide corresponding to hamster PrP residues 119 to 136, which was identical in both mouse and hamster PrP, was able to inhibit PrP-res formation in both the mouse and hamster cell-free systems as well as in scrapie-infected mouse neuroblastoma cell cultures. Because the PrP region from 119 to 136 is very conserved in most species, this peptide may have inhibitory effects on PrP conversion in a wide variety of TSE diseases.

* Corresponding author. Mailing address: NIH, NIAID, Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, 903 South 4th St., Hamilton, MT 59840. Phone: (406) 363-9354. Fax: (406) 363-9286. E-mail: bchesebro{at}nih.gov.

dagger Present address: IPMC, CNRS, 06560 Valbonne, France.

Dagger Present address: Institute for Animal Health, Compton Laboratory, Compton, Nr. Newbury, Berkshire RG20 7NN, United Kingdom.

Journal of Virology, August 1999, p. 6245-6250, Vol. 73, No. 8
0022-538X/99/$04.00+0


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