Search for a prion-specific nucleic acid.
Identifieur interne : 002320 ( PubMed/Curation ); précédent : 002319; suivant : 002321Search for a prion-specific nucleic acid.
Auteurs : Jiri G. Safar [États-Unis] ; Klaus Kellings ; Ana Serban ; Darlene Groth ; James E. Cleaver ; Stanley B. Prusiner ; Detlev RiesnerSource :
- Journal of virology [ 0022-538X ] ; 2005.
Descripteurs français
- KwdFr :
- MESH :
- analyse : ARN, Acides nucléiques.
- effets des radiations : Prions.
- génétique : Prions.
- métabolisme : Encéphale, Prions.
- pharmacologie : Zinc, Éthanol.
- Animaux, Centrifugation en gradient de densité, Cricetinae, Mesocricetus, Rayons ultraviolets.
English descriptors
- KwdEn :
- MESH :
- chemical , analysis : Nucleic Acids, RNA.
- chemical , genetics : Prions.
- chemical , metabolism : Prions.
- chemical , pharmacology : Ethanol, Zinc.
- metabolism : Brain.
- chemical , radiation effects : Prions.
- Animals, Centrifugation, Density Gradient, Cricetinae, Mesocricetus, Ultraviolet Rays.
Abstract
Diversity of prion strains was attributed to an elusive nucleic acid, yet a search spanning nearly two decades has failed to identify a prion-specific polynucleotide. In our search for a prion-specific nucleic acid, we analyzed nucleic acids in purified fractions from the brains of Syrian hamsters infected with Sc237 prions. Purification of Sc237 prions removed nucleic acids larger than 50 nucleotides as measured by return refocusing electrophoresis (RRGE). To determine the size of the largest polynucleotide present in purified fractions at an abundance of one molecule per infectious (ID50) unit, we measured prions present after inoculation. In order to account for the rapid clearance of prions after intracerebral inoculation, we determined the number of PrP(Sc) molecules and ID50 units of prions that were retained in brain. Factoring in clearance after inoculation, we estimate that the largest polynucleotide present in our purified fractions at one molecule per ID50 unit is approximately 25 nucleotides in length. In the same fractions, there were approximately 3,000 protease-resistant PrP(Sc) molecules per ID50 unit after accounting for clearance of PrP(Sc) following inoculation. We compared the resistance of Sc237 and 139H prions to inactivation by UV irradiation at 254 nm. Irradiation of homogenates and microsomes diminished prion infectivity by a factor of approximately 1,000 but did not alter the strain-specified properties of the Sc237 and 139H prions. The data reported here combined with the production of synthetic prions argue that the 25-mer polynucleotides found in purified prion preparations are likely to be host encoded and of variable sequence; additionally, these 25-mers are unlikely to be prion specific.
DOI: 10.1128/JVI.79.16.10796-10806.2005
PubMed: 16051871
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Safar</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Neurodegenerative Diseases, University of California, San Francisco 94143-0518, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute for Neurodegenerative Diseases, University of California, San Francisco 94143-0518</wicri:regionArea></affiliation></author><author><name sortKey="Kellings, Klaus" sort="Kellings, Klaus" uniqKey="Kellings K" first="Klaus" last="Kellings">Klaus Kellings</name></author><author><name sortKey="Serban, Ana" sort="Serban, Ana" uniqKey="Serban A" first="Ana" last="Serban">Ana Serban</name></author><author><name sortKey="Groth, Darlene" sort="Groth, Darlene" uniqKey="Groth D" first="Darlene" last="Groth">Darlene Groth</name></author><author><name sortKey="Cleaver, James E" sort="Cleaver, James E" uniqKey="Cleaver J" first="James E" last="Cleaver">James E. 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Safar</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Neurodegenerative Diseases, University of California, San Francisco 94143-0518, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute for Neurodegenerative Diseases, University of California, San Francisco 94143-0518</wicri:regionArea></affiliation></author><author><name sortKey="Kellings, Klaus" sort="Kellings, Klaus" uniqKey="Kellings K" first="Klaus" last="Kellings">Klaus Kellings</name></author><author><name sortKey="Serban, Ana" sort="Serban, Ana" uniqKey="Serban A" first="Ana" last="Serban">Ana Serban</name></author><author><name sortKey="Groth, Darlene" sort="Groth, Darlene" uniqKey="Groth D" first="Darlene" last="Groth">Darlene Groth</name></author><author><name sortKey="Cleaver, James E" sort="Cleaver, James E" uniqKey="Cleaver J" first="James E" last="Cleaver">James E. 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Prusiner</name></author><author><name sortKey="Riesner, Detlev" sort="Riesner, Detlev" uniqKey="Riesner D" first="Detlev" last="Riesner">Detlev Riesner</name></author></analytic><series><title level="j">Journal of virology</title><idno type="ISSN">0022-538X</idno><imprint><date when="2005" type="published">2005</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Brain (metabolism)</term><term>Centrifugation, Density Gradient</term><term>Cricetinae</term><term>Ethanol (pharmacology)</term><term>Mesocricetus</term><term>Nucleic Acids (analysis)</term><term>Prions (genetics)</term><term>Prions (metabolism)</term><term>Prions (radiation effects)</term><term>RNA (analysis)</term><term>Ultraviolet Rays</term><term>Zinc (pharmacology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN (analyse)</term><term>Acides nucléiques (analyse)</term><term>Animaux</term><term>Centrifugation en gradient de densité</term><term>Cricetinae</term><term>Encéphale (métabolisme)</term><term>Mesocricetus</term><term>Prions (effets des radiations)</term><term>Prions (génétique)</term><term>Prions (métabolisme)</term><term>Rayons ultraviolets</term><term>Zinc (pharmacologie)</term><term>Éthanol (pharmacologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Nucleic Acids</term><term>RNA</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Prions</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Prions</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Ethanol</term><term>Zinc</term></keywords><keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>ARN</term><term>Acides nucléiques</term></keywords><keywords scheme="MESH" qualifier="effets des radiations" xml:lang="fr"><term>Prions</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Prions</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Encéphale</term><term>Prions</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Zinc</term><term>Éthanol</term></keywords><keywords scheme="MESH" type="chemical" qualifier="radiation effects" xml:lang="en"><term>Prions</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Centrifugation, Density Gradient</term><term>Cricetinae</term><term>Mesocricetus</term><term>Ultraviolet Rays</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Centrifugation en gradient de densité</term><term>Cricetinae</term><term>Mesocricetus</term><term>Rayons ultraviolets</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Diversity of prion strains was attributed to an elusive nucleic acid, yet a search spanning nearly two decades has failed to identify a prion-specific polynucleotide. In our search for a prion-specific nucleic acid, we analyzed nucleic acids in purified fractions from the brains of Syrian hamsters infected with Sc237 prions. Purification of Sc237 prions removed nucleic acids larger than 50 nucleotides as measured by return refocusing electrophoresis (RRGE). To determine the size of the largest polynucleotide present in purified fractions at an abundance of one molecule per infectious (ID50) unit, we measured prions present after inoculation. In order to account for the rapid clearance of prions after intracerebral inoculation, we determined the number of PrP(Sc) molecules and ID50 units of prions that were retained in brain. Factoring in clearance after inoculation, we estimate that the largest polynucleotide present in our purified fractions at one molecule per ID50 unit is approximately 25 nucleotides in length. In the same fractions, there were approximately 3,000 protease-resistant PrP(Sc) molecules per ID50 unit after accounting for clearance of PrP(Sc) following inoculation. We compared the resistance of Sc237 and 139H prions to inactivation by UV irradiation at 254 nm. Irradiation of homogenates and microsomes diminished prion infectivity by a factor of approximately 1,000 but did not alter the strain-specified properties of the Sc237 and 139H prions. The data reported here combined with the production of synthetic prions argue that the 25-mer polynucleotides found in purified prion preparations are likely to be host encoded and of variable sequence; additionally, these 25-mers are unlikely to be prion specific.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">16051871</PMID><DateCompleted><Year>2005</Year><Month>09</Month><Day>08</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0022-538X</ISSN><JournalIssue CitedMedium="Print"><Volume>79</Volume><Issue>16</Issue><PubDate><Year>2005</Year><Month>Aug</Month></PubDate></JournalIssue><Title>Journal of virology</Title><ISOAbbreviation>J. Virol.</ISOAbbreviation></Journal><ArticleTitle>Search for a prion-specific nucleic acid.</ArticleTitle><Pagination><MedlinePgn>10796-806</MedlinePgn></Pagination><Abstract><AbstractText>Diversity of prion strains was attributed to an elusive nucleic acid, yet a search spanning nearly two decades has failed to identify a prion-specific polynucleotide. In our search for a prion-specific nucleic acid, we analyzed nucleic acids in purified fractions from the brains of Syrian hamsters infected with Sc237 prions. Purification of Sc237 prions removed nucleic acids larger than 50 nucleotides as measured by return refocusing electrophoresis (RRGE). To determine the size of the largest polynucleotide present in purified fractions at an abundance of one molecule per infectious (ID50) unit, we measured prions present after inoculation. In order to account for the rapid clearance of prions after intracerebral inoculation, we determined the number of PrP(Sc) molecules and ID50 units of prions that were retained in brain. Factoring in clearance after inoculation, we estimate that the largest polynucleotide present in our purified fractions at one molecule per ID50 unit is approximately 25 nucleotides in length. In the same fractions, there were approximately 3,000 protease-resistant PrP(Sc) molecules per ID50 unit after accounting for clearance of PrP(Sc) following inoculation. We compared the resistance of Sc237 and 139H prions to inactivation by UV irradiation at 254 nm. Irradiation of homogenates and microsomes diminished prion infectivity by a factor of approximately 1,000 but did not alter the strain-specified properties of the Sc237 and 139H prions. The data reported here combined with the production of synthetic prions argue that the 25-mer polynucleotides found in purified prion preparations are likely to be host encoded and of variable sequence; additionally, these 25-mers are unlikely to be prion specific.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Safar</LastName><ForeName>Jiri G</ForeName><Initials>JG</Initials><AffiliationInfo><Affiliation>Institute for Neurodegenerative Diseases, University of California, San Francisco 94143-0518, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kellings</LastName><ForeName>Klaus</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Serban</LastName><ForeName>Ana</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Groth</LastName><ForeName>Darlene</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Cleaver</LastName><ForeName>James E</ForeName><Initials>JE</Initials></Author><Author ValidYN="Y"><LastName>Prusiner</LastName><ForeName>Stanley B</ForeName><Initials>SB</Initials></Author><Author ValidYN="Y"><LastName>Riesner</LastName><ForeName>Detlev</ForeName><Initials>D</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>P01 AG002132</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P01 AG010770</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P01 AG021601</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AG021601</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AG02132</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United 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