Systematic, genome-wide identification of host genes affecting replication of a positive-strand RNA virus.
Identifieur interne : 000503 ( Ncbi/Merge ); précédent : 000502; suivant : 000504Systematic, genome-wide identification of host genes affecting replication of a positive-strand RNA virus.
Auteurs : David B. Kushner [États-Unis] ; Brett D. Lindenbach ; Valery Z. Grdzelishvili ; Amine O. Noueiry ; Scott M. Paul ; Paul AhlquistSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2003.
Descripteurs français
- KwdFr :
- ARN viral (génétique), Bromovirus (génétique), Coronavirus (génétique), Enzymes (génétique), Génome viral, Hepacivirus (génétique), Humains, Protéines virales (génétique), Réplication virale (génétique), Virus à ARN (enzymologie), Virus à ARN (génétique), Virus à ARN (pathogénicité), Virus à ARN (physiologie).
- MESH :
- enzymologie : Virus à ARN.
- génétique : ARN viral, Bromovirus, Coronavirus, Enzymes, Hepacivirus, Protéines virales, Réplication virale, Virus à ARN.
- pathogénicité : Virus à ARN.
- physiologie : Virus à ARN.
- Génome viral, Humains.
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Enzymes, RNA, Viral, Viral Proteins.
- enzymology : RNA Viruses.
- genetics : Bromovirus, Coronavirus, Hepacivirus, RNA Viruses, Virus Replication.
- pathogenicity : RNA Viruses.
- physiology : RNA Viruses.
- Genome, Viral, Humans.
Abstract
Positive-strand RNA viruses are the largest virus class and include many pathogens such as hepatitis C virus and the severe acute respiratory syndrome coronavirus (SARS). Brome mosaic virus (BMV) is a representative positive-strand RNA virus whose RNA replication, gene expression, and encapsidation have been reproduced in the yeast Saccharomyces cerevisiae. By using traditional yeast genetics, host genes have been identified that function in controlling BMV translation, selecting BMV RNAs as replication templates, activating the replication complex, maintaining a lipid composition required for membrane-associated RNA replication, and other steps. To more globally and systematically identify such host factors, we used engineered BMV derivatives to assay viral RNA replication in each strain of an ordered, genome-wide set of yeast single-gene deletion mutants. Each deletion strain was transformed to express BMV replicase proteins and a BMV RNA replication template with the capsid gene replaced by a luciferase reporter. Luciferase expression, which is dependent on viral RNA replication and RNA-dependent mRNA synthesis, was measured in intact yeast cells. Approximately 4500 yeast deletion strains ( approximately 80% of yeast genes) were screened in duplicate and selected strains analyzed further. This functional genomics approach revealed nearly 100 genes whose absence inhibited or stimulated BMV RNA replication and/or gene expression by 3- to >25-fold. Several of these genes were shown previously to function in BMV replication, validating the approach. Newly identified genes include some in RNA, protein, or membrane modification pathways and genes of unknown function. The results further illuminate virus and cell pathways. Further refinement of virus screening likely will reveal contributions from additional host genes.
DOI: 10.1073/pnas.2536857100
PubMed: 14671320
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Kushner</name><affiliation wicri:level="2"><nlm:affiliation>Institute for Molecular Virology and Howard Hughes Medical Institute, University of Wisconsin, Madison, WI 53706, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute for Molecular Virology and Howard Hughes Medical Institute, University of Wisconsin, Madison, WI 53706</wicri:regionArea><placeName><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Lindenbach, Brett D" sort="Lindenbach, Brett D" uniqKey="Lindenbach B" first="Brett D" last="Lindenbach">Brett D. Lindenbach</name></author><author><name sortKey="Grdzelishvili, Valery Z" sort="Grdzelishvili, Valery Z" uniqKey="Grdzelishvili V" first="Valery Z" last="Grdzelishvili">Valery Z. Grdzelishvili</name></author><author><name sortKey="Noueiry, Amine O" sort="Noueiry, Amine O" uniqKey="Noueiry A" first="Amine O" last="Noueiry">Amine O. 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Paul</name></author><author><name sortKey="Ahlquist, Paul" sort="Ahlquist, Paul" uniqKey="Ahlquist P" first="Paul" last="Ahlquist">Paul Ahlquist</name></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><imprint><date when="2003" type="published">2003</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Bromovirus (genetics)</term><term>Coronavirus (genetics)</term><term>Enzymes (genetics)</term><term>Genome, Viral</term><term>Hepacivirus (genetics)</term><term>Humans</term><term>RNA Viruses (enzymology)</term><term>RNA Viruses (genetics)</term><term>RNA Viruses (pathogenicity)</term><term>RNA Viruses (physiology)</term><term>RNA, Viral (genetics)</term><term>Viral Proteins (genetics)</term><term>Virus Replication (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN viral (génétique)</term><term>Bromovirus (génétique)</term><term>Coronavirus (génétique)</term><term>Enzymes (génétique)</term><term>Génome viral</term><term>Hepacivirus (génétique)</term><term>Humains</term><term>Protéines virales (génétique)</term><term>Réplication virale (génétique)</term><term>Virus à ARN (enzymologie)</term><term>Virus à ARN (génétique)</term><term>Virus à ARN (pathogénicité)</term><term>Virus à ARN (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Enzymes</term><term>RNA, Viral</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Virus à ARN</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>RNA Viruses</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Bromovirus</term><term>Coronavirus</term><term>Hepacivirus</term><term>RNA Viruses</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ARN viral</term><term>Bromovirus</term><term>Coronavirus</term><term>Enzymes</term><term>Hepacivirus</term><term>Protéines virales</term><term>Réplication virale</term><term>Virus à ARN</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>RNA Viruses</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus à ARN</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus à ARN</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>RNA Viruses</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Genome, Viral</term><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Génome viral</term><term>Humains</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Positive-strand RNA viruses are the largest virus class and include many pathogens such as hepatitis C virus and the severe acute respiratory syndrome coronavirus (SARS). Brome mosaic virus (BMV) is a representative positive-strand RNA virus whose RNA replication, gene expression, and encapsidation have been reproduced in the yeast Saccharomyces cerevisiae. By using traditional yeast genetics, host genes have been identified that function in controlling BMV translation, selecting BMV RNAs as replication templates, activating the replication complex, maintaining a lipid composition required for membrane-associated RNA replication, and other steps. To more globally and systematically identify such host factors, we used engineered BMV derivatives to assay viral RNA replication in each strain of an ordered, genome-wide set of yeast single-gene deletion mutants. Each deletion strain was transformed to express BMV replicase proteins and a BMV RNA replication template with the capsid gene replaced by a luciferase reporter. Luciferase expression, which is dependent on viral RNA replication and RNA-dependent mRNA synthesis, was measured in intact yeast cells. Approximately 4500 yeast deletion strains ( approximately 80% of yeast genes) were screened in duplicate and selected strains analyzed further. This functional genomics approach revealed nearly 100 genes whose absence inhibited or stimulated BMV RNA replication and/or gene expression by 3- to >25-fold. Several of these genes were shown previously to function in BMV replication, validating the approach. Newly identified genes include some in RNA, protein, or membrane modification pathways and genes of unknown function. The results further illuminate virus and cell pathways. Further refinement of virus screening likely will reveal contributions from additional host genes.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">14671320</PMID><DateCompleted><Year>2004</Year><Month>04</Month><Day>20</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Print">0027-8424</ISSN><JournalIssue CitedMedium="Print"><Volume>100</Volume><Issue>26</Issue><PubDate><Year>2003</Year><Month>Dec</Month><Day>23</Day></PubDate></JournalIssue><Title>Proceedings of the National Academy of Sciences of the United States of America</Title><ISOAbbreviation>Proc. Natl. Acad. Sci. U.S.A.</ISOAbbreviation></Journal><ArticleTitle>Systematic, genome-wide identification of host genes affecting replication of a positive-strand RNA virus.</ArticleTitle><Pagination><MedlinePgn>15764-9</MedlinePgn></Pagination><Abstract><AbstractText>Positive-strand RNA viruses are the largest virus class and include many pathogens such as hepatitis C virus and the severe acute respiratory syndrome coronavirus (SARS). Brome mosaic virus (BMV) is a representative positive-strand RNA virus whose RNA replication, gene expression, and encapsidation have been reproduced in the yeast Saccharomyces cerevisiae. By using traditional yeast genetics, host genes have been identified that function in controlling BMV translation, selecting BMV RNAs as replication templates, activating the replication complex, maintaining a lipid composition required for membrane-associated RNA replication, and other steps. To more globally and systematically identify such host factors, we used engineered BMV derivatives to assay viral RNA replication in each strain of an ordered, genome-wide set of yeast single-gene deletion mutants. Each deletion strain was transformed to express BMV replicase proteins and a BMV RNA replication template with the capsid gene replaced by a luciferase reporter. Luciferase expression, which is dependent on viral RNA replication and RNA-dependent mRNA synthesis, was measured in intact yeast cells. Approximately 4500 yeast deletion strains ( approximately 80% of yeast genes) were screened in duplicate and selected strains analyzed further. This functional genomics approach revealed nearly 100 genes whose absence inhibited or stimulated BMV RNA replication and/or gene expression by 3- to >25-fold. Several of these genes were shown previously to function in BMV replication, validating the approach. Newly identified genes include some in RNA, protein, or membrane modification pathways and genes of unknown function. The results further illuminate virus and cell pathways. Further refinement of virus screening likely will reveal contributions from additional host genes.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kushner</LastName><ForeName>David B</ForeName><Initials>DB</Initials><AffiliationInfo><Affiliation>Institute for Molecular Virology and Howard Hughes Medical Institute, University of Wisconsin, Madison, WI 53706, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lindenbach</LastName><ForeName>Brett D</ForeName><Initials>BD</Initials></Author><Author ValidYN="Y"><LastName>Grdzelishvili</LastName><ForeName>Valery Z</ForeName><Initials>VZ</Initials></Author><Author ValidYN="Y"><LastName>Noueiry</LastName><ForeName>Amine O</ForeName><Initials>AO</Initials></Author><Author ValidYN="Y"><LastName>Paul</LastName><ForeName>Scott M</ForeName><Initials>SM</Initials></Author><Author ValidYN="Y"><LastName>Ahlquist</LastName><ForeName>Paul</ForeName><Initials>P</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 GM035072</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R37 GM035072</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32 CA009075</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32 CA09075</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D013487">Research Support, U.S. Gov't, P.H.S.</PublicationType></PublicationTypeList><ArticleDate 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sortKey="Grdzelishvili, Valery Z" sort="Grdzelishvili, Valery Z" uniqKey="Grdzelishvili V" first="Valery Z" last="Grdzelishvili">Valery Z. Grdzelishvili</name><name sortKey="Lindenbach, Brett D" sort="Lindenbach, Brett D" uniqKey="Lindenbach B" first="Brett D" last="Lindenbach">Brett D. Lindenbach</name><name sortKey="Noueiry, Amine O" sort="Noueiry, Amine O" uniqKey="Noueiry A" first="Amine O" last="Noueiry">Amine O. Noueiry</name><name sortKey="Paul, Scott M" sort="Paul, Scott M" uniqKey="Paul S" first="Scott M" last="Paul">Scott M. Paul</name></noCountry><country name="États-Unis"><region name="Wisconsin"><name sortKey="Kushner, David B" sort="Kushner, David B" uniqKey="Kushner D" first="David B" last="Kushner">David B. Kushner</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|area= SrasV1
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|clé= pubmed:14671320
|texte= Systematic, genome-wide identification of host genes affecting replication of a positive-strand RNA virus.
}}
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