De novo generation of infectious prions in vitro produces a new disease phenotype.

Prions are the proteinaceous infectious agents responsible for Transmissible Spongiform Encephalopathies. Compelling evidence supports the hypothesis that prions are composed exclusively of a misfolded version of the prion protein (PrP(Sc)) that replicates in the body in the absence of nucleic acids...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Marcelo A Barria [verfasserIn] Abhisek Mukherjee [verfasserIn] Dennisse Gonzalez-Romero [verfasserIn] Rodrigo Morales [verfasserIn] Claudio Soto [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2009

Übergeordnetes Werk:	In: PLoS Pathogens - Public Library of Science (PLoS), 2005, 5(2009), 5, p e1000421
Übergeordnetes Werk:	volume:5 ; year:2009 ; number:5, p e1000421

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.1371/journal.ppat.1000421

Katalog-ID:	DOAJ044491026

Internformat


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520			\|a Prions are the proteinaceous infectious agents responsible for Transmissible Spongiform Encephalopathies. Compelling evidence supports the hypothesis that prions are composed exclusively of a misfolded version of the prion protein (PrP(Sc)) that replicates in the body in the absence of nucleic acids by inducing the misfolding of the cellular prion protein (PrP(C)). The most common form of human prion disease is sporadic, which appears to have its origin in a low frequency event of spontaneous misfolding to generate the first PrP(Sc) particle that then propagates as in the infectious form of the disease. The main goal of this study was to mimic an early event in the etiology of sporadic disease by attempting de novo generation of infectious PrP(Sc)in vitro. For this purpose we analyzed in detail the possibility of spontaneous generation of PrP(Sc) by the protein misfolding cyclic amplification (PMCA) procedure. Under standard PMCA conditions, and taking precautions to avoid cross-contamination, de novo generation of PrP(Sc) was never observed, supporting the use of the technology for diagnostic applications. However, we report that PMCA can be modified to generate PrP(Sc) in the absence of pre-existing PrP(Sc) in different animal species at a low and variable rate. De novo generated PrP(Sc) was infectious when inoculated into wild type hamsters, producing a new disease phenotype with unique clinical, neuropathological and biochemical features. Our results represent additional evidence in support of the prion hypothesis and provide a simple model to study the mechanism of sporadic prion disease. The findings also suggest that prion diversity is not restricted to those currently known, and that likely new forms of infectious protein foldings may be produced, resulting in novel disease phenotypes.
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publishDate	2009
allfields	10.1371/journal.ppat.1000421 doi (DE-627)DOAJ044491026 (DE-599)DOAJecd47b99c52e46c4a8daf61678fe231e DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Marcelo A Barria verfasserin aut De novo generation of infectious prions in vitro produces a new disease phenotype. 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Prions are the proteinaceous infectious agents responsible for Transmissible Spongiform Encephalopathies. Compelling evidence supports the hypothesis that prions are composed exclusively of a misfolded version of the prion protein (PrP(Sc)) that replicates in the body in the absence of nucleic acids by inducing the misfolding of the cellular prion protein (PrP(C)). The most common form of human prion disease is sporadic, which appears to have its origin in a low frequency event of spontaneous misfolding to generate the first PrP(Sc) particle that then propagates as in the infectious form of the disease. The main goal of this study was to mimic an early event in the etiology of sporadic disease by attempting de novo generation of infectious PrP(Sc)in vitro. For this purpose we analyzed in detail the possibility of spontaneous generation of PrP(Sc) by the protein misfolding cyclic amplification (PMCA) procedure. Under standard PMCA conditions, and taking precautions to avoid cross-contamination, de novo generation of PrP(Sc) was never observed, supporting the use of the technology for diagnostic applications. However, we report that PMCA can be modified to generate PrP(Sc) in the absence of pre-existing PrP(Sc) in different animal species at a low and variable rate. De novo generated PrP(Sc) was infectious when inoculated into wild type hamsters, producing a new disease phenotype with unique clinical, neuropathological and biochemical features. Our results represent additional evidence in support of the prion hypothesis and provide a simple model to study the mechanism of sporadic prion disease. The findings also suggest that prion diversity is not restricted to those currently known, and that likely new forms of infectious protein foldings may be produced, resulting in novel disease phenotypes. Immunologic diseases. Allergy Biology (General) Abhisek Mukherjee verfasserin aut Dennisse Gonzalez-Romero verfasserin aut Rodrigo Morales verfasserin aut Claudio Soto verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 5(2009), 5, p e1000421 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:5 year:2009 number:5, p e1000421 https://doi.org/10.1371/journal.ppat.1000421 kostenfrei https://doaj.org/article/ecd47b99c52e46c4a8daf61678fe231e kostenfrei http://europepmc.org/articles/PMC2675078?pdf=render kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2009 5, p e1000421
spelling	10.1371/journal.ppat.1000421 doi (DE-627)DOAJ044491026 (DE-599)DOAJecd47b99c52e46c4a8daf61678fe231e DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Marcelo A Barria verfasserin aut De novo generation of infectious prions in vitro produces a new disease phenotype. 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Prions are the proteinaceous infectious agents responsible for Transmissible Spongiform Encephalopathies. Compelling evidence supports the hypothesis that prions are composed exclusively of a misfolded version of the prion protein (PrP(Sc)) that replicates in the body in the absence of nucleic acids by inducing the misfolding of the cellular prion protein (PrP(C)). The most common form of human prion disease is sporadic, which appears to have its origin in a low frequency event of spontaneous misfolding to generate the first PrP(Sc) particle that then propagates as in the infectious form of the disease. The main goal of this study was to mimic an early event in the etiology of sporadic disease by attempting de novo generation of infectious PrP(Sc)in vitro. For this purpose we analyzed in detail the possibility of spontaneous generation of PrP(Sc) by the protein misfolding cyclic amplification (PMCA) procedure. Under standard PMCA conditions, and taking precautions to avoid cross-contamination, de novo generation of PrP(Sc) was never observed, supporting the use of the technology for diagnostic applications. However, we report that PMCA can be modified to generate PrP(Sc) in the absence of pre-existing PrP(Sc) in different animal species at a low and variable rate. De novo generated PrP(Sc) was infectious when inoculated into wild type hamsters, producing a new disease phenotype with unique clinical, neuropathological and biochemical features. Our results represent additional evidence in support of the prion hypothesis and provide a simple model to study the mechanism of sporadic prion disease. The findings also suggest that prion diversity is not restricted to those currently known, and that likely new forms of infectious protein foldings may be produced, resulting in novel disease phenotypes. Immunologic diseases. Allergy Biology (General) Abhisek Mukherjee verfasserin aut Dennisse Gonzalez-Romero verfasserin aut Rodrigo Morales verfasserin aut Claudio Soto verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 5(2009), 5, p e1000421 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:5 year:2009 number:5, p e1000421 https://doi.org/10.1371/journal.ppat.1000421 kostenfrei https://doaj.org/article/ecd47b99c52e46c4a8daf61678fe231e kostenfrei http://europepmc.org/articles/PMC2675078?pdf=render kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2009 5, p e1000421
allfields_unstemmed	10.1371/journal.ppat.1000421 doi (DE-627)DOAJ044491026 (DE-599)DOAJecd47b99c52e46c4a8daf61678fe231e DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Marcelo A Barria verfasserin aut De novo generation of infectious prions in vitro produces a new disease phenotype. 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Prions are the proteinaceous infectious agents responsible for Transmissible Spongiform Encephalopathies. Compelling evidence supports the hypothesis that prions are composed exclusively of a misfolded version of the prion protein (PrP(Sc)) that replicates in the body in the absence of nucleic acids by inducing the misfolding of the cellular prion protein (PrP(C)). The most common form of human prion disease is sporadic, which appears to have its origin in a low frequency event of spontaneous misfolding to generate the first PrP(Sc) particle that then propagates as in the infectious form of the disease. The main goal of this study was to mimic an early event in the etiology of sporadic disease by attempting de novo generation of infectious PrP(Sc)in vitro. For this purpose we analyzed in detail the possibility of spontaneous generation of PrP(Sc) by the protein misfolding cyclic amplification (PMCA) procedure. Under standard PMCA conditions, and taking precautions to avoid cross-contamination, de novo generation of PrP(Sc) was never observed, supporting the use of the technology for diagnostic applications. However, we report that PMCA can be modified to generate PrP(Sc) in the absence of pre-existing PrP(Sc) in different animal species at a low and variable rate. De novo generated PrP(Sc) was infectious when inoculated into wild type hamsters, producing a new disease phenotype with unique clinical, neuropathological and biochemical features. Our results represent additional evidence in support of the prion hypothesis and provide a simple model to study the mechanism of sporadic prion disease. The findings also suggest that prion diversity is not restricted to those currently known, and that likely new forms of infectious protein foldings may be produced, resulting in novel disease phenotypes. Immunologic diseases. Allergy Biology (General) Abhisek Mukherjee verfasserin aut Dennisse Gonzalez-Romero verfasserin aut Rodrigo Morales verfasserin aut Claudio Soto verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 5(2009), 5, p e1000421 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:5 year:2009 number:5, p e1000421 https://doi.org/10.1371/journal.ppat.1000421 kostenfrei https://doaj.org/article/ecd47b99c52e46c4a8daf61678fe231e kostenfrei http://europepmc.org/articles/PMC2675078?pdf=render kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2009 5, p e1000421
allfieldsGer	10.1371/journal.ppat.1000421 doi (DE-627)DOAJ044491026 (DE-599)DOAJecd47b99c52e46c4a8daf61678fe231e DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Marcelo A Barria verfasserin aut De novo generation of infectious prions in vitro produces a new disease phenotype. 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Prions are the proteinaceous infectious agents responsible for Transmissible Spongiform Encephalopathies. Compelling evidence supports the hypothesis that prions are composed exclusively of a misfolded version of the prion protein (PrP(Sc)) that replicates in the body in the absence of nucleic acids by inducing the misfolding of the cellular prion protein (PrP(C)). The most common form of human prion disease is sporadic, which appears to have its origin in a low frequency event of spontaneous misfolding to generate the first PrP(Sc) particle that then propagates as in the infectious form of the disease. The main goal of this study was to mimic an early event in the etiology of sporadic disease by attempting de novo generation of infectious PrP(Sc)in vitro. For this purpose we analyzed in detail the possibility of spontaneous generation of PrP(Sc) by the protein misfolding cyclic amplification (PMCA) procedure. Under standard PMCA conditions, and taking precautions to avoid cross-contamination, de novo generation of PrP(Sc) was never observed, supporting the use of the technology for diagnostic applications. However, we report that PMCA can be modified to generate PrP(Sc) in the absence of pre-existing PrP(Sc) in different animal species at a low and variable rate. De novo generated PrP(Sc) was infectious when inoculated into wild type hamsters, producing a new disease phenotype with unique clinical, neuropathological and biochemical features. Our results represent additional evidence in support of the prion hypothesis and provide a simple model to study the mechanism of sporadic prion disease. The findings also suggest that prion diversity is not restricted to those currently known, and that likely new forms of infectious protein foldings may be produced, resulting in novel disease phenotypes. Immunologic diseases. Allergy Biology (General) Abhisek Mukherjee verfasserin aut Dennisse Gonzalez-Romero verfasserin aut Rodrigo Morales verfasserin aut Claudio Soto verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 5(2009), 5, p e1000421 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:5 year:2009 number:5, p e1000421 https://doi.org/10.1371/journal.ppat.1000421 kostenfrei https://doaj.org/article/ecd47b99c52e46c4a8daf61678fe231e kostenfrei http://europepmc.org/articles/PMC2675078?pdf=render kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2009 5, p e1000421
allfieldsSound	10.1371/journal.ppat.1000421 doi (DE-627)DOAJ044491026 (DE-599)DOAJecd47b99c52e46c4a8daf61678fe231e DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Marcelo A Barria verfasserin aut De novo generation of infectious prions in vitro produces a new disease phenotype. 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Prions are the proteinaceous infectious agents responsible for Transmissible Spongiform Encephalopathies. Compelling evidence supports the hypothesis that prions are composed exclusively of a misfolded version of the prion protein (PrP(Sc)) that replicates in the body in the absence of nucleic acids by inducing the misfolding of the cellular prion protein (PrP(C)). The most common form of human prion disease is sporadic, which appears to have its origin in a low frequency event of spontaneous misfolding to generate the first PrP(Sc) particle that then propagates as in the infectious form of the disease. The main goal of this study was to mimic an early event in the etiology of sporadic disease by attempting de novo generation of infectious PrP(Sc)in vitro. For this purpose we analyzed in detail the possibility of spontaneous generation of PrP(Sc) by the protein misfolding cyclic amplification (PMCA) procedure. Under standard PMCA conditions, and taking precautions to avoid cross-contamination, de novo generation of PrP(Sc) was never observed, supporting the use of the technology for diagnostic applications. However, we report that PMCA can be modified to generate PrP(Sc) in the absence of pre-existing PrP(Sc) in different animal species at a low and variable rate. De novo generated PrP(Sc) was infectious when inoculated into wild type hamsters, producing a new disease phenotype with unique clinical, neuropathological and biochemical features. Our results represent additional evidence in support of the prion hypothesis and provide a simple model to study the mechanism of sporadic prion disease. The findings also suggest that prion diversity is not restricted to those currently known, and that likely new forms of infectious protein foldings may be produced, resulting in novel disease phenotypes. Immunologic diseases. Allergy Biology (General) Abhisek Mukherjee verfasserin aut Dennisse Gonzalez-Romero verfasserin aut Rodrigo Morales verfasserin aut Claudio Soto verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 5(2009), 5, p e1000421 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:5 year:2009 number:5, p e1000421 https://doi.org/10.1371/journal.ppat.1000421 kostenfrei https://doaj.org/article/ecd47b99c52e46c4a8daf61678fe231e kostenfrei http://europepmc.org/articles/PMC2675078?pdf=render kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2009 5, p e1000421
language	English
source	In PLoS Pathogens 5(2009), 5, p e1000421 volume:5 year:2009 number:5, p e1000421
sourceStr	In PLoS Pathogens 5(2009), 5, p e1000421 volume:5 year:2009 number:5, p e1000421
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Immunologic diseases. Allergy Biology (General)
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container_title	PLoS Pathogens
authorswithroles_txt_mv	Marcelo A Barria @@aut@@ Abhisek Mukherjee @@aut@@ Dennisse Gonzalez-Romero @@aut@@ Rodrigo Morales @@aut@@ Claudio Soto @@aut@@
publishDateDaySort_date	2009-01-01T00:00:00Z
hierarchy_top_id	501074422
id	DOAJ044491026
language_de	englisch
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callnumber-first	R - Medicine
author	Marcelo A Barria
spellingShingle	Marcelo A Barria misc RC581-607 misc QH301-705.5 misc Immunologic diseases. Allergy misc Biology (General) De novo generation of infectious prions in vitro produces a new disease phenotype.
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topic_title	RC581-607 QH301-705.5 De novo generation of infectious prions in vitro produces a new disease phenotype
topic	misc RC581-607 misc QH301-705.5 misc Immunologic diseases. Allergy misc Biology (General)
topic_unstemmed	misc RC581-607 misc QH301-705.5 misc Immunologic diseases. Allergy misc Biology (General)
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title	De novo generation of infectious prions in vitro produces a new disease phenotype.
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title_full	De novo generation of infectious prions in vitro produces a new disease phenotype
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title_sort	novo generation of infectious prions in vitro produces a new disease phenotype
callnumber	RC581-607
title_auth	De novo generation of infectious prions in vitro produces a new disease phenotype.
abstract	Prions are the proteinaceous infectious agents responsible for Transmissible Spongiform Encephalopathies. Compelling evidence supports the hypothesis that prions are composed exclusively of a misfolded version of the prion protein (PrP(Sc)) that replicates in the body in the absence of nucleic acids by inducing the misfolding of the cellular prion protein (PrP(C)). The most common form of human prion disease is sporadic, which appears to have its origin in a low frequency event of spontaneous misfolding to generate the first PrP(Sc) particle that then propagates as in the infectious form of the disease. The main goal of this study was to mimic an early event in the etiology of sporadic disease by attempting de novo generation of infectious PrP(Sc)in vitro. For this purpose we analyzed in detail the possibility of spontaneous generation of PrP(Sc) by the protein misfolding cyclic amplification (PMCA) procedure. Under standard PMCA conditions, and taking precautions to avoid cross-contamination, de novo generation of PrP(Sc) was never observed, supporting the use of the technology for diagnostic applications. However, we report that PMCA can be modified to generate PrP(Sc) in the absence of pre-existing PrP(Sc) in different animal species at a low and variable rate. De novo generated PrP(Sc) was infectious when inoculated into wild type hamsters, producing a new disease phenotype with unique clinical, neuropathological and biochemical features. Our results represent additional evidence in support of the prion hypothesis and provide a simple model to study the mechanism of sporadic prion disease. The findings also suggest that prion diversity is not restricted to those currently known, and that likely new forms of infectious protein foldings may be produced, resulting in novel disease phenotypes.
abstractGer	Prions are the proteinaceous infectious agents responsible for Transmissible Spongiform Encephalopathies. Compelling evidence supports the hypothesis that prions are composed exclusively of a misfolded version of the prion protein (PrP(Sc)) that replicates in the body in the absence of nucleic acids by inducing the misfolding of the cellular prion protein (PrP(C)). The most common form of human prion disease is sporadic, which appears to have its origin in a low frequency event of spontaneous misfolding to generate the first PrP(Sc) particle that then propagates as in the infectious form of the disease. The main goal of this study was to mimic an early event in the etiology of sporadic disease by attempting de novo generation of infectious PrP(Sc)in vitro. For this purpose we analyzed in detail the possibility of spontaneous generation of PrP(Sc) by the protein misfolding cyclic amplification (PMCA) procedure. Under standard PMCA conditions, and taking precautions to avoid cross-contamination, de novo generation of PrP(Sc) was never observed, supporting the use of the technology for diagnostic applications. However, we report that PMCA can be modified to generate PrP(Sc) in the absence of pre-existing PrP(Sc) in different animal species at a low and variable rate. De novo generated PrP(Sc) was infectious when inoculated into wild type hamsters, producing a new disease phenotype with unique clinical, neuropathological and biochemical features. Our results represent additional evidence in support of the prion hypothesis and provide a simple model to study the mechanism of sporadic prion disease. The findings also suggest that prion diversity is not restricted to those currently known, and that likely new forms of infectious protein foldings may be produced, resulting in novel disease phenotypes.
abstract_unstemmed	Prions are the proteinaceous infectious agents responsible for Transmissible Spongiform Encephalopathies. Compelling evidence supports the hypothesis that prions are composed exclusively of a misfolded version of the prion protein (PrP(Sc)) that replicates in the body in the absence of nucleic acids by inducing the misfolding of the cellular prion protein (PrP(C)). The most common form of human prion disease is sporadic, which appears to have its origin in a low frequency event of spontaneous misfolding to generate the first PrP(Sc) particle that then propagates as in the infectious form of the disease. The main goal of this study was to mimic an early event in the etiology of sporadic disease by attempting de novo generation of infectious PrP(Sc)in vitro. For this purpose we analyzed in detail the possibility of spontaneous generation of PrP(Sc) by the protein misfolding cyclic amplification (PMCA) procedure. Under standard PMCA conditions, and taking precautions to avoid cross-contamination, de novo generation of PrP(Sc) was never observed, supporting the use of the technology for diagnostic applications. However, we report that PMCA can be modified to generate PrP(Sc) in the absence of pre-existing PrP(Sc) in different animal species at a low and variable rate. De novo generated PrP(Sc) was infectious when inoculated into wild type hamsters, producing a new disease phenotype with unique clinical, neuropathological and biochemical features. Our results represent additional evidence in support of the prion hypothesis and provide a simple model to study the mechanism of sporadic prion disease. The findings also suggest that prion diversity is not restricted to those currently known, and that likely new forms of infectious protein foldings may be produced, resulting in novel disease phenotypes.
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title_short	De novo generation of infectious prions in vitro produces a new disease phenotype.
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De novo generation of infectious prions in vitro produces a new disease phenotype.

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