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Accelerated high fidelity prion amplification within and across prion species barriers
Experimental obstacles have impeded our ability to study prion transmission within and, more particularly, between species. Here, we used cervid prion protein expressed in brain extracts of transgenic mice, referred to as Tg(CerPrP), as a substrate for in vitro generation of chronic wasting disease...
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Published in: | PLoS pathogens 2008-08, Vol.4 (8), p.e1000139-e1000139 |
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description | Experimental obstacles have impeded our ability to study prion transmission within and, more particularly, between species. Here, we used cervid prion protein expressed in brain extracts of transgenic mice, referred to as Tg(CerPrP), as a substrate for in vitro generation of chronic wasting disease (CWD) prions by protein misfolding cyclic amplification (PMCA). Characterization of this infectivity in Tg(CerPrP) mice demonstrated that serial PMCA resulted in the high fidelity amplification of CWD prions with apparently unaltered properties. Using similar methods to amplify mouse RML prions and characterize the resulting novel cervid prions, we show that serial PMCA abrogated a transmission barrier that required several hundred days of adaptation and subsequent stabilization in Tg(CerPrP) mice. While both approaches produced cervid prions with characteristics distinct from CWD, the subtly different properties of the resulting individual prion isolates indicated that adaptation of mouse RML prions generated multiple strains following inter-species transmission. Our studies demonstrate that combined transgenic mouse and PMCA approaches not only expedite intra- and inter-species prion transmission, but also provide a facile means of generating and characterizing novel prion strains. |
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Here, we used cervid prion protein expressed in brain extracts of transgenic mice, referred to as Tg(CerPrP), as a substrate for in vitro generation of chronic wasting disease (CWD) prions by protein misfolding cyclic amplification (PMCA). Characterization of this infectivity in Tg(CerPrP) mice demonstrated that serial PMCA resulted in the high fidelity amplification of CWD prions with apparently unaltered properties. Using similar methods to amplify mouse RML prions and characterize the resulting novel cervid prions, we show that serial PMCA abrogated a transmission barrier that required several hundred days of adaptation and subsequent stabilization in Tg(CerPrP) mice. While both approaches produced cervid prions with characteristics distinct from CWD, the subtly different properties of the resulting individual prion isolates indicated that adaptation of mouse RML prions generated multiple strains following inter-species transmission. Our studies demonstrate that combined transgenic mouse and PMCA approaches not only expedite intra- and inter-species prion transmission, but also provide a facile means of generating and characterizing novel prion strains.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1000139</identifier><identifier>PMID: 18769716</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Brain ; Creutzfeldt-Jakob disease ; Deer ; Development and progression ; Disease transmission ; Distribution ; Female ; Genetic aspects ; Immunization ; Infectious Diseases/Prion Diseases ; Mice ; Mice, Transgenic ; Pathogenesis ; Physiological aspects ; Prion diseases ; Prions ; Prions - metabolism ; Protein Folding ; Proteins ; Public health ; Risk factors ; Sheep ; Species Specificity ; Spongiform encephalopathies ; Studies ; Wasting Disease, Chronic - metabolism ; Wasting Disease, Chronic - pathology ; Wasting Disease, Chronic - transmission</subject><ispartof>PLoS pathogens, 2008-08, Vol.4 (8), p.e1000139-e1000139</ispartof><rights>COPYRIGHT 2008 Public Library of Science</rights><rights>Green et al. 2008</rights><rights>2008 Green et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Green KM, Castilla J, Seward TS, Napier DL, Jewell JE, et al. (2008) Accelerated High Fidelity Prion Amplification Within and Across Prion Species Barriers. PLoS Pathog 4(8): e1000139. doi:10.1371/journal.ppat.1000139</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c697t-b78bd9f04c2ed1c076467d7e086a31fcd9a64f7a88e219a9edb642a75bb91f9e3</citedby><cites>FETCH-LOGICAL-c697t-b78bd9f04c2ed1c076467d7e086a31fcd9a64f7a88e219a9edb642a75bb91f9e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2516356/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2516356/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,733,786,790,891,27957,27958,37048,53827,53829</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18769716$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Mabbott, Neil</contributor><creatorcontrib>Green, Kristi M</creatorcontrib><creatorcontrib>Castilla, Joaquín</creatorcontrib><creatorcontrib>Seward, Tanya S</creatorcontrib><creatorcontrib>Napier, Dana L</creatorcontrib><creatorcontrib>Jewell, Jean E</creatorcontrib><creatorcontrib>Soto, Claudio</creatorcontrib><creatorcontrib>Telling, Glenn C</creatorcontrib><title>Accelerated high fidelity prion amplification within and across prion species barriers</title><title>PLoS pathogens</title><addtitle>PLoS Pathog</addtitle><description>Experimental obstacles have impeded our ability to study prion transmission within and, more particularly, between species. Here, we used cervid prion protein expressed in brain extracts of transgenic mice, referred to as Tg(CerPrP), as a substrate for in vitro generation of chronic wasting disease (CWD) prions by protein misfolding cyclic amplification (PMCA). Characterization of this infectivity in Tg(CerPrP) mice demonstrated that serial PMCA resulted in the high fidelity amplification of CWD prions with apparently unaltered properties. Using similar methods to amplify mouse RML prions and characterize the resulting novel cervid prions, we show that serial PMCA abrogated a transmission barrier that required several hundred days of adaptation and subsequent stabilization in Tg(CerPrP) mice. While both approaches produced cervid prions with characteristics distinct from CWD, the subtly different properties of the resulting individual prion isolates indicated that adaptation of mouse RML prions generated multiple strains following inter-species transmission. Our studies demonstrate that combined transgenic mouse and PMCA approaches not only expedite intra- and inter-species prion transmission, but also provide a facile means of generating and characterizing novel prion strains.</description><subject>Animals</subject><subject>Brain</subject><subject>Creutzfeldt-Jakob disease</subject><subject>Deer</subject><subject>Development and progression</subject><subject>Disease transmission</subject><subject>Distribution</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Immunization</subject><subject>Infectious Diseases/Prion Diseases</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Pathogenesis</subject><subject>Physiological aspects</subject><subject>Prion diseases</subject><subject>Prions</subject><subject>Prions - metabolism</subject><subject>Protein Folding</subject><subject>Proteins</subject><subject>Public health</subject><subject>Risk factors</subject><subject>Sheep</subject><subject>Species Specificity</subject><subject>Spongiform encephalopathies</subject><subject>Studies</subject><subject>Wasting Disease, Chronic - metabolism</subject><subject>Wasting Disease, Chronic - pathology</subject><subject>Wasting Disease, Chronic - transmission</subject><issn>1553-7374</issn><issn>1553-7366</issn><issn>1553-7374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNqVkk2LFDEQhhtR3HX1H4g2CIKHGZNOd9K5CMPix8Ci4Nc1VCeVmQw9nTbJqPvvTe-0ugNeJIcklafeKipvUTymZEmZoC93_hAG6JfjCGlJCSGUyTvFOW0athBM1Hdvnc-KBzHuCKkpo_x-cUZbwaWg_Lz4utIaewyQ0JRbt9mW1hnsXboux-D8UMJ-7J11GtJ0--HS1uXgYErQwcc4U3FE7TCWHYTgMMSHxT0LfcRH835RfHnz-vPlu8XVh7fry9XVQuf6adGJtjPSklpXaKgmgtdcGIGk5cCo1UYCr62AtsWKSpBoOl5XIJquk9RKZBfF06Pu2Puo5pFERatWEla3lGZifSSMh53K3e4hXCsPTt0EfNgoCMnpHhUTndC2aohosG7butOEGCJ5owkXRPOs9Wquduj2aDQOKUB_Inr6Mrit2vjvqmooZ80k8HwWCP7bAWNSexfz_HsY0B-i4jKDvJIZfHYEN5Abc4P1WU9PsFpVhFWsomSSW_6Dysvg3mk_oHU5fpLw4iQhMwl_pg0cYlTrTx__g31_ytZH9sYTAe2fmVCiJrf-_ho1uVXNbs1pT27P82_SbE_2C8zO5rA</recordid><startdate>20080801</startdate><enddate>20080801</enddate><creator>Green, Kristi M</creator><creator>Castilla, Joaquín</creator><creator>Seward, Tanya S</creator><creator>Napier, Dana L</creator><creator>Jewell, Jean E</creator><creator>Soto, Claudio</creator><creator>Telling, Glenn C</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISN</scope><scope>ISR</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20080801</creationdate><title>Accelerated high fidelity prion amplification within and across prion species barriers</title><author>Green, Kristi M ; Castilla, Joaquín ; Seward, Tanya S ; Napier, Dana L ; Jewell, Jean E ; Soto, Claudio ; Telling, Glenn C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c697t-b78bd9f04c2ed1c076467d7e086a31fcd9a64f7a88e219a9edb642a75bb91f9e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Brain</topic><topic>Creutzfeldt-Jakob disease</topic><topic>Deer</topic><topic>Development and progression</topic><topic>Disease transmission</topic><topic>Distribution</topic><topic>Female</topic><topic>Genetic aspects</topic><topic>Immunization</topic><topic>Infectious Diseases/Prion Diseases</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Pathogenesis</topic><topic>Physiological aspects</topic><topic>Prion diseases</topic><topic>Prions</topic><topic>Prions - metabolism</topic><topic>Protein Folding</topic><topic>Proteins</topic><topic>Public health</topic><topic>Risk factors</topic><topic>Sheep</topic><topic>Species Specificity</topic><topic>Spongiform encephalopathies</topic><topic>Studies</topic><topic>Wasting Disease, Chronic - metabolism</topic><topic>Wasting Disease, Chronic - pathology</topic><topic>Wasting Disease, Chronic - transmission</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Green, Kristi M</creatorcontrib><creatorcontrib>Castilla, Joaquín</creatorcontrib><creatorcontrib>Seward, Tanya S</creatorcontrib><creatorcontrib>Napier, Dana L</creatorcontrib><creatorcontrib>Jewell, Jean E</creatorcontrib><creatorcontrib>Soto, Claudio</creatorcontrib><creatorcontrib>Telling, Glenn C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS pathogens</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Green, Kristi M</au><au>Castilla, Joaquín</au><au>Seward, Tanya S</au><au>Napier, Dana L</au><au>Jewell, Jean E</au><au>Soto, Claudio</au><au>Telling, Glenn C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Accelerated high fidelity prion amplification within and across prion species barriers</atitle><jtitle>PLoS pathogens</jtitle><addtitle>PLoS Pathog</addtitle><date>2008-08-01</date><risdate>2008</risdate><volume>4</volume><issue>8</issue><spage>e1000139</spage><epage>e1000139</epage><pages>e1000139-e1000139</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><notes>Conceived and designed the experiments: KMG JC CS GCT. Performed the experiments: KMG JC TSS DLN. Analyzed the data: KMG JC CS GCT. Contributed reagents/materials/analysis tools: JEJ. Wrote the paper: KMG JC GCT.</notes><notes>b: Current address: Department of Infectology, Scripps Research Institute, Jupiter, Florida, United States of America</notes><notes>a: Current address: Department of Neurology, University of Texas Medical Branch, Galveston, Texas, United States of America</notes><abstract>Experimental obstacles have impeded our ability to study prion transmission within and, more particularly, between species. Here, we used cervid prion protein expressed in brain extracts of transgenic mice, referred to as Tg(CerPrP), as a substrate for in vitro generation of chronic wasting disease (CWD) prions by protein misfolding cyclic amplification (PMCA). Characterization of this infectivity in Tg(CerPrP) mice demonstrated that serial PMCA resulted in the high fidelity amplification of CWD prions with apparently unaltered properties. Using similar methods to amplify mouse RML prions and characterize the resulting novel cervid prions, we show that serial PMCA abrogated a transmission barrier that required several hundred days of adaptation and subsequent stabilization in Tg(CerPrP) mice. While both approaches produced cervid prions with characteristics distinct from CWD, the subtly different properties of the resulting individual prion isolates indicated that adaptation of mouse RML prions generated multiple strains following inter-species transmission. Our studies demonstrate that combined transgenic mouse and PMCA approaches not only expedite intra- and inter-species prion transmission, but also provide a facile means of generating and characterizing novel prion strains.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>18769716</pmid><doi>10.1371/journal.ppat.1000139</doi><oa>free_for_read</oa></addata></record> |
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subjects | Animals Brain Creutzfeldt-Jakob disease Deer Development and progression Disease transmission Distribution Female Genetic aspects Immunization Infectious Diseases/Prion Diseases Mice Mice, Transgenic Pathogenesis Physiological aspects Prion diseases Prions Prions - metabolism Protein Folding Proteins Public health Risk factors Sheep Species Specificity Spongiform encephalopathies Studies Wasting Disease, Chronic - metabolism Wasting Disease, Chronic - pathology Wasting Disease, Chronic - transmission |
title | Accelerated high fidelity prion amplification within and across prion species barriers |
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