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Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins
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| Zeitschriftentitel: | Journal of Virology |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , |
| In: | Journal of Virology, 86, 2012, 21, S. 11763-11778 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society for Microbiology
|
| Schlagwörter: |
| author_facet |
Raymond, Gregory J. Race, Brent Hollister, Jason R. Offerdahl, Danielle K. Moore, Roger A. Kodali, Ravindra Raymond, Lynne D. Hughson, Andrew G. Rosenke, Rebecca Long, Dan Dorward, David W. Baron, Gerald S. Raymond, Gregory J. Race, Brent Hollister, Jason R. Offerdahl, Danielle K. Moore, Roger A. Kodali, Ravindra Raymond, Lynne D. Hughson, Andrew G. Rosenke, Rebecca Long, Dan Dorward, David W. Baron, Gerald S. |
|---|---|
| author |
Raymond, Gregory J. Race, Brent Hollister, Jason R. Offerdahl, Danielle K. Moore, Roger A. Kodali, Ravindra Raymond, Lynne D. Hughson, Andrew G. Rosenke, Rebecca Long, Dan Dorward, David W. Baron, Gerald S. |
| spellingShingle |
Raymond, Gregory J. Race, Brent Hollister, Jason R. Offerdahl, Danielle K. Moore, Roger A. Kodali, Ravindra Raymond, Lynne D. Hughson, Andrew G. Rosenke, Rebecca Long, Dan Dorward, David W. Baron, Gerald S. Journal of Virology Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins Virology Insect Science Immunology Microbiology |
| author_sort |
raymond, gregory j. |
| spelling |
Raymond, Gregory J. Race, Brent Hollister, Jason R. Offerdahl, Danielle K. Moore, Roger A. Kodali, Ravindra Raymond, Lynne D. Hughson, Andrew G. Rosenke, Rebecca Long, Dan Dorward, David W. Baron, Gerald S. 0022-538X 1098-5514 American Society for Microbiology Virology Insect Science Immunology Microbiology http://dx.doi.org/10.1128/jvi.01353-12 <jats:title>ABSTRACT</jats:title> <jats:p> Mammalian prions are thought to consist of misfolded aggregates (protease-resistant isoform of the prion protein [PrP <jats:sup>res</jats:sup> ]) of the cellular prion protein (PrP <jats:sup>C</jats:sup> ). Transmissible spongiform encephalopathy (TSE) can be induced in animals inoculated with recombinant PrP (rPrP) amyloid fibrils lacking mammalian posttranslational modifications, but this induction is inefficient in hamsters or transgenic mice overexpressing glycosylphosphatidylinositol (GPI)-anchored PrP <jats:sup>C</jats:sup> . Here we show that TSE can be initiated by inoculation of misfolded rPrP into mice that express wild-type (wt) levels of PrP <jats:sup>C</jats:sup> and that synthetic prion strain propagation and selection can be affected by GPI anchoring of the host's PrP <jats:sup>C</jats:sup> . To create prions <jats:italic>de novo</jats:italic> , we fibrillized mouse rPrP in the absence of molecular cofactors, generating fibrils with a PrP <jats:sup>res</jats:sup> -like protease-resistant banding profile. These fibrils induced the formation of PrP <jats:sup>res</jats:sup> deposits in transgenic mice coexpressing wt and GPI-anchorless PrP <jats:sup>C</jats:sup> (wt/GPI <jats:sup>−</jats:sup> ) at a combined level comparable to that of PrP <jats:sup>C</jats:sup> expression in wt mice. Secondary passage into mice expressing wt, GPI <jats:sup>−</jats:sup> , or wt plus GPI <jats:sup>−</jats:sup> PrP <jats:sup>C</jats:sup> induced TSE disease with novel clinical, histopathological, and biochemical phenotypes. Contrary to laboratory-adapted mouse scrapie strains, the synthetic prion agents exhibited a preference for conversion of GPI <jats:sup>−</jats:sup> PrP <jats:sup>C</jats:sup> and, in one case, caused disease only in GPI <jats:sup>−</jats:sup> mice. Our data show that novel TSE agents can be generated <jats:italic>de novo</jats:italic> solely from purified mouse rPrP after amplification in mice coexpressing normal levels of wt and anchorless PrP <jats:sup>C</jats:sup> . These observations provide insight into the minimal elements required to create prions <jats:italic>in vitro</jats:italic> and suggest that the PrP <jats:sup>C</jats:sup> GPI anchor can modulate the propagation of synthetic TSE strains. </jats:p> Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins Journal of Virology |
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American Society for Microbiology, 2012 |
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2012 |
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American Society for Microbiology |
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Journal of Virology |
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49 |
| title |
Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins |
| title_unstemmed |
Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins |
| title_full |
Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins |
| title_fullStr |
Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins |
| title_full_unstemmed |
Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins |
| title_short |
Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins |
| title_sort |
isolation of novel synthetic prion strains by amplification in transgenic mice coexpressing wild-type and anchorless prion proteins |
| topic |
Virology Insect Science Immunology Microbiology |
| url |
http://dx.doi.org/10.1128/jvi.01353-12 |
| publishDate |
2012 |
| physical |
11763-11778 |
| description |
<jats:title>ABSTRACT</jats:title>
<jats:p>
Mammalian prions are thought to consist of misfolded aggregates (protease-resistant isoform of the prion protein [PrP
<jats:sup>res</jats:sup>
]) of the cellular prion protein (PrP
<jats:sup>C</jats:sup>
). Transmissible spongiform encephalopathy (TSE) can be induced in animals inoculated with recombinant PrP (rPrP) amyloid fibrils lacking mammalian posttranslational modifications, but this induction is inefficient in hamsters or transgenic mice overexpressing glycosylphosphatidylinositol (GPI)-anchored PrP
<jats:sup>C</jats:sup>
. Here we show that TSE can be initiated by inoculation of misfolded rPrP into mice that express wild-type (wt) levels of PrP
<jats:sup>C</jats:sup>
and that synthetic prion strain propagation and selection can be affected by GPI anchoring of the host's PrP
<jats:sup>C</jats:sup>
. To create prions
<jats:italic>de novo</jats:italic>
, we fibrillized mouse rPrP in the absence of molecular cofactors, generating fibrils with a PrP
<jats:sup>res</jats:sup>
-like protease-resistant banding profile. These fibrils induced the formation of PrP
<jats:sup>res</jats:sup>
deposits in transgenic mice coexpressing wt and GPI-anchorless PrP
<jats:sup>C</jats:sup>
(wt/GPI
<jats:sup>−</jats:sup>
) at a combined level comparable to that of PrP
<jats:sup>C</jats:sup>
expression in wt mice. Secondary passage into mice expressing wt, GPI
<jats:sup>−</jats:sup>
, or wt plus GPI
<jats:sup>−</jats:sup>
PrP
<jats:sup>C</jats:sup>
induced TSE disease with novel clinical, histopathological, and biochemical phenotypes. Contrary to laboratory-adapted mouse scrapie strains, the synthetic prion agents exhibited a preference for conversion of GPI
<jats:sup>−</jats:sup>
PrP
<jats:sup>C</jats:sup>
and, in one case, caused disease only in GPI
<jats:sup>−</jats:sup>
mice. Our data show that novel TSE agents can be generated
<jats:italic>de novo</jats:italic>
solely from purified mouse rPrP after amplification in mice coexpressing normal levels of wt and anchorless PrP
<jats:sup>C</jats:sup>
. These observations provide insight into the minimal elements required to create prions
<jats:italic>in vitro</jats:italic>
and suggest that the PrP
<jats:sup>C</jats:sup>
GPI anchor can modulate the propagation of synthetic TSE strains.
</jats:p> |
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| author | Raymond, Gregory J., Race, Brent, Hollister, Jason R., Offerdahl, Danielle K., Moore, Roger A., Kodali, Ravindra, Raymond, Lynne D., Hughson, Andrew G., Rosenke, Rebecca, Long, Dan, Dorward, David W., Baron, Gerald S. |
| author_facet | Raymond, Gregory J., Race, Brent, Hollister, Jason R., Offerdahl, Danielle K., Moore, Roger A., Kodali, Ravindra, Raymond, Lynne D., Hughson, Andrew G., Rosenke, Rebecca, Long, Dan, Dorward, David W., Baron, Gerald S., Raymond, Gregory J., Race, Brent, Hollister, Jason R., Offerdahl, Danielle K., Moore, Roger A., Kodali, Ravindra, Raymond, Lynne D., Hughson, Andrew G., Rosenke, Rebecca, Long, Dan, Dorward, David W., Baron, Gerald S. |
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| description | <jats:title>ABSTRACT</jats:title> <jats:p> Mammalian prions are thought to consist of misfolded aggregates (protease-resistant isoform of the prion protein [PrP <jats:sup>res</jats:sup> ]) of the cellular prion protein (PrP <jats:sup>C</jats:sup> ). Transmissible spongiform encephalopathy (TSE) can be induced in animals inoculated with recombinant PrP (rPrP) amyloid fibrils lacking mammalian posttranslational modifications, but this induction is inefficient in hamsters or transgenic mice overexpressing glycosylphosphatidylinositol (GPI)-anchored PrP <jats:sup>C</jats:sup> . Here we show that TSE can be initiated by inoculation of misfolded rPrP into mice that express wild-type (wt) levels of PrP <jats:sup>C</jats:sup> and that synthetic prion strain propagation and selection can be affected by GPI anchoring of the host's PrP <jats:sup>C</jats:sup> . To create prions <jats:italic>de novo</jats:italic> , we fibrillized mouse rPrP in the absence of molecular cofactors, generating fibrils with a PrP <jats:sup>res</jats:sup> -like protease-resistant banding profile. These fibrils induced the formation of PrP <jats:sup>res</jats:sup> deposits in transgenic mice coexpressing wt and GPI-anchorless PrP <jats:sup>C</jats:sup> (wt/GPI <jats:sup>−</jats:sup> ) at a combined level comparable to that of PrP <jats:sup>C</jats:sup> expression in wt mice. Secondary passage into mice expressing wt, GPI <jats:sup>−</jats:sup> , or wt plus GPI <jats:sup>−</jats:sup> PrP <jats:sup>C</jats:sup> induced TSE disease with novel clinical, histopathological, and biochemical phenotypes. Contrary to laboratory-adapted mouse scrapie strains, the synthetic prion agents exhibited a preference for conversion of GPI <jats:sup>−</jats:sup> PrP <jats:sup>C</jats:sup> and, in one case, caused disease only in GPI <jats:sup>−</jats:sup> mice. Our data show that novel TSE agents can be generated <jats:italic>de novo</jats:italic> solely from purified mouse rPrP after amplification in mice coexpressing normal levels of wt and anchorless PrP <jats:sup>C</jats:sup> . These observations provide insight into the minimal elements required to create prions <jats:italic>in vitro</jats:italic> and suggest that the PrP <jats:sup>C</jats:sup> GPI anchor can modulate the propagation of synthetic TSE strains. </jats:p> |
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| spelling | Raymond, Gregory J. Race, Brent Hollister, Jason R. Offerdahl, Danielle K. Moore, Roger A. Kodali, Ravindra Raymond, Lynne D. Hughson, Andrew G. Rosenke, Rebecca Long, Dan Dorward, David W. Baron, Gerald S. 0022-538X 1098-5514 American Society for Microbiology Virology Insect Science Immunology Microbiology http://dx.doi.org/10.1128/jvi.01353-12 <jats:title>ABSTRACT</jats:title> <jats:p> Mammalian prions are thought to consist of misfolded aggregates (protease-resistant isoform of the prion protein [PrP <jats:sup>res</jats:sup> ]) of the cellular prion protein (PrP <jats:sup>C</jats:sup> ). Transmissible spongiform encephalopathy (TSE) can be induced in animals inoculated with recombinant PrP (rPrP) amyloid fibrils lacking mammalian posttranslational modifications, but this induction is inefficient in hamsters or transgenic mice overexpressing glycosylphosphatidylinositol (GPI)-anchored PrP <jats:sup>C</jats:sup> . Here we show that TSE can be initiated by inoculation of misfolded rPrP into mice that express wild-type (wt) levels of PrP <jats:sup>C</jats:sup> and that synthetic prion strain propagation and selection can be affected by GPI anchoring of the host's PrP <jats:sup>C</jats:sup> . To create prions <jats:italic>de novo</jats:italic> , we fibrillized mouse rPrP in the absence of molecular cofactors, generating fibrils with a PrP <jats:sup>res</jats:sup> -like protease-resistant banding profile. These fibrils induced the formation of PrP <jats:sup>res</jats:sup> deposits in transgenic mice coexpressing wt and GPI-anchorless PrP <jats:sup>C</jats:sup> (wt/GPI <jats:sup>−</jats:sup> ) at a combined level comparable to that of PrP <jats:sup>C</jats:sup> expression in wt mice. Secondary passage into mice expressing wt, GPI <jats:sup>−</jats:sup> , or wt plus GPI <jats:sup>−</jats:sup> PrP <jats:sup>C</jats:sup> induced TSE disease with novel clinical, histopathological, and biochemical phenotypes. Contrary to laboratory-adapted mouse scrapie strains, the synthetic prion agents exhibited a preference for conversion of GPI <jats:sup>−</jats:sup> PrP <jats:sup>C</jats:sup> and, in one case, caused disease only in GPI <jats:sup>−</jats:sup> mice. Our data show that novel TSE agents can be generated <jats:italic>de novo</jats:italic> solely from purified mouse rPrP after amplification in mice coexpressing normal levels of wt and anchorless PrP <jats:sup>C</jats:sup> . These observations provide insight into the minimal elements required to create prions <jats:italic>in vitro</jats:italic> and suggest that the PrP <jats:sup>C</jats:sup> GPI anchor can modulate the propagation of synthetic TSE strains. </jats:p> Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins Journal of Virology |
| spellingShingle | Raymond, Gregory J., Race, Brent, Hollister, Jason R., Offerdahl, Danielle K., Moore, Roger A., Kodali, Ravindra, Raymond, Lynne D., Hughson, Andrew G., Rosenke, Rebecca, Long, Dan, Dorward, David W., Baron, Gerald S., Journal of Virology, Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins, Virology, Insect Science, Immunology, Microbiology |
| title | Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins |
| title_full | Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins |
| title_fullStr | Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins |
| title_full_unstemmed | Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins |
| title_short | Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins |
| title_sort | isolation of novel synthetic prion strains by amplification in transgenic mice coexpressing wild-type and anchorless prion proteins |
| title_unstemmed | Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins |
| topic | Virology, Insect Science, Immunology, Microbiology |
| url | http://dx.doi.org/10.1128/jvi.01353-12 |