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Journal of Virology, January 2001, p. 107-114, Vol. 75, No. 1
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.1.107-114.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Molecular Analysis of the Abnormal Prion Protein
during Coinfection of Mice by Bovine Spongiform Encephalopathy
and a Scrapie Agent
Thierry G. M.
Baron1,* and
Anne-Gaelle
Biacabe1,2
Agence Française de
Sécurité Sanitaire des Aliments1 and
Hôpital Neurologique de Lyon,2
Lyon, France
Received 24 August 2000/Accepted 2 October 2000
Molecular features of the proteinase K-resistant prion protein (PrP
res) may discriminate among prion strains, and a specific signature
could be found during infection by the infectious agent causing bovine
spongiform encephalopathy (BSE). To investigate the molecular basis of
BSE adaptation and selection, we established a model of coinfection of
mice by both BSE and a sheep scrapie strain (C506M3). We now show that
the PrP res features in these mice, characterized by glycoform ratios
and electrophoretic mobilities, may be undistinguishable from those
found in mice infected with scrapie only, including when mice were
inoculated by both strains at the same time and by the same
intracerebral inoculation route. Western blot analysis using different
antibodies against sequences near the putative N-terminal end of PrP
res also demonstrated differences in the main proteinase K cleavage
sites between mice showing either the BSE or scrapie PrP res profile.
These results, which may be linked to higher levels of PrP res
associated with infection by scrapie, were similar following a
challenge by a higher dose of the BSE agent during coinfection by both
strains intracerebrally. Whereas PrP res extraction methods used
allowed us to distinguish type 1 and type 2 PrP res, differing, like
BSE and scrapie, by their electrophoretic mobilities, in the same brain
region of some patients with Creutzfeldt-Jakob disease, analysis of in
vitro mixtures of BSE and scrapie brain homogenates did not allow us to
distinguish BSE and scrapie PrP res. These results suggest that the BSE
agent, the origin of which remains unknown so far but which may have
arisen from a sheep scrapie agent, may be hidden by a scrapie strain
during attempts to identify it by molecular studies and following
transmission of the disease in mice.
*
Corresponding author. Mailing address: AFSSA-Lyon, 31 ave. Tony Garnier, 69364 Lyon cedex 07, France. Phone: (33) (4)
78-72-65-43. Fax: (33) (4) 78-61-91-45. E-mail:
t.baron{at}lyon.afssa.fr.
Journal of Virology, January 2001, p. 107-114, Vol. 75, No. 1
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.1.107-114.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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