High fidelity of murine hepatitis virus replication is decreased in nsp14 exoribonuclease mutants
Identifieur interne : 000661 ( PascalFrancis/Curation ); précédent : 000660; suivant : 000662High fidelity of murine hepatitis virus replication is decreased in nsp14 exoribonuclease mutants
Auteurs : Lance D. Eckerle [États-Unis] ; XIAOTAO LU [États-Unis] ; Steven M. Sperry [États-Unis] ; Leena Choi [États-Unis] ; Mark R. Denison [États-Unis]Source :
- Journal of virology [ 0022-538X ] ; 2007.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Replication fidelity of RNA virus genomes is constrained by the opposing necessities of generating sufficient diversity for adaptation and maintaining genetic stability, but it is unclear how the largest viral RNA genomes have evolved and are maintained under these constraints. A coronavirus (CoV) nonstructural protein, nsp14, contains conserved active-site motifs of cellular exonucleases, including DNA proofreading enzymes, and the severe acute respiratory syndrome CoV (SARS-CoV) nsp14 has 3'-to-5' exoribonuclease (ExoN) activity in vitro. Here, we show that nsp14 ExoN remarkably increases replication fidelity of the CoV murine hepatitis virus (MHV). Replacement of conserved MHV ExoN active-site residues with alanines resulted in viable mutant viruses with growth and RNA synthesis defects that during passage accumulated 15-fold more mutations than wild-type virus without changes in growth fitness. The estimated mutation rate for ExoN mutants was similar to that reported for other RNA viruses, whereas that of wild-type MHV was less than the established rates for RNA viruses in general, suggesting that CoVs with intact ExoN replicate with unusually high fidelity. Our results indicate that nspl4 ExoN plays a critical role in prevention or repair of nucleotide incorporation errors during genome replication. The established mutants are unique tools to test the hypothesis that high replication fidelity is required for the evolution and stability of large RNA genomes.
| pA |
|
|---|
Links toward previous steps (curation, corpus...)
- to stream PascalFrancis, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000328
Links to Exploration step
Pascal:07-0517249Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">High fidelity of murine hepatitis virus replication is decreased in nsp14 exoribonuclease mutants</title><author><name sortKey="Eckerle, Lance D" sort="Eckerle, Lance D" uniqKey="Eckerle L" first="Lance D." last="Eckerle">Lance D. Eckerle</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pediatrics, Microbiology, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Immunology, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Xiaotao Lu" sort="Xiaotao Lu" uniqKey="Xiaotao Lu" last="Xiaotao Lu">XIAOTAO LU</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pediatrics, Microbiology, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Sperry, Steven M" sort="Sperry, Steven M" uniqKey="Sperry S" first="Steven M." last="Sperry">Steven M. Sperry</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pediatrics, Microbiology, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Choi, Leena" sort="Choi, Leena" uniqKey="Choi L" first="Leena" last="Choi">Leena Choi</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Biostatistics, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R." last="Denison">Mark R. Denison</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pediatrics, Microbiology, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Immunology, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">07-0517249</idno><date when="2007">2007</date><idno type="stanalyst">PASCAL 07-0517249 INIST</idno><idno type="RBID">Pascal:07-0517249</idno><idno type="wicri:Area/PascalFrancis/Corpus">000328</idno><idno type="wicri:Area/PascalFrancis/Curation">000661</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">High fidelity of murine hepatitis virus replication is decreased in nsp14 exoribonuclease mutants</title><author><name sortKey="Eckerle, Lance D" sort="Eckerle, Lance D" uniqKey="Eckerle L" first="Lance D." last="Eckerle">Lance D. Eckerle</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pediatrics, Microbiology, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Immunology, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Xiaotao Lu" sort="Xiaotao Lu" uniqKey="Xiaotao Lu" last="Xiaotao Lu">XIAOTAO LU</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pediatrics, Microbiology, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Sperry, Steven M" sort="Sperry, Steven M" uniqKey="Sperry S" first="Steven M." last="Sperry">Steven M. Sperry</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pediatrics, Microbiology, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Choi, Leena" sort="Choi, Leena" uniqKey="Choi L" first="Leena" last="Choi">Leena Choi</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Biostatistics, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R." last="Denison">Mark R. Denison</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pediatrics, Microbiology, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Immunology, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author></analytic><series><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Exoribonuclease</term><term>Murine hepatitis virus</term><term>Mutation</term><term>Replication</term><term>Virology</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Virus hépatite murine</term><term>Réplication</term><term>Exoribonuclease</term><term>Mutation</term><term>Virologie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Replication fidelity of RNA virus genomes is constrained by the opposing necessities of generating sufficient diversity for adaptation and maintaining genetic stability, but it is unclear how the largest viral RNA genomes have evolved and are maintained under these constraints. A coronavirus (CoV) nonstructural protein, nsp14, contains conserved active-site motifs of cellular exonucleases, including DNA proofreading enzymes, and the severe acute respiratory syndrome CoV (SARS-CoV) nsp14 has 3'-to-5' exoribonuclease (ExoN) activity in vitro. Here, we show that nsp14 ExoN remarkably increases replication fidelity of the CoV murine hepatitis virus (MHV). Replacement of conserved MHV ExoN active-site residues with alanines resulted in viable mutant viruses with growth and RNA synthesis defects that during passage accumulated 15-fold more mutations than wild-type virus without changes in growth fitness. The estimated mutation rate for ExoN mutants was similar to that reported for other RNA viruses, whereas that of wild-type MHV was less than the established rates for RNA viruses in general, suggesting that CoVs with intact ExoN replicate with unusually high fidelity. Our results indicate that nspl4 ExoN plays a critical role in prevention or repair of nucleotide incorporation errors during genome replication. The established mutants are unique tools to test the hypothesis that high replication fidelity is required for the evolution and stability of large RNA genomes.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0022-538X</s0></fA01><fA03 i2="1"><s0>J. virol.</s0></fA03><fA05><s2>81</s2></fA05><fA06><s2>22</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>High fidelity of murine hepatitis virus replication is decreased in nsp14 exoribonuclease mutants</s1></fA08><fA11 i1="01" i2="1"><s1>ECKERLE (Lance D.)</s1></fA11><fA11 i1="02" i2="1"><s1>XIAOTAO LU</s1></fA11><fA11 i1="03" i2="1"><s1>SPERRY (Steven M.)</s1></fA11><fA11 i1="04" i2="1"><s1>CHOI (Leena)</s1></fA11><fA11 i1="05" i2="1"><s1>DENISON (Mark R.)</s1></fA11><fA14 i1="01"><s1>Department of Pediatrics, Microbiology, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></fA14><fA14 i1="02"><s1>Department of Immunology, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ></fA14><fA14 i1="03"><s1>Department of Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></fA14><fA14 i1="04"><s1>Department of Biostatistics, Vanderbilt University Medical Center</s1><s2>Nashville, Tennessee 37232</s2><s3>USA</s3><sZ>4 aut.</sZ></fA14><fA20><s1>12135-12144</s1></fA20><fA21><s1>2007</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>13592</s2><s5>354000173476840050</s5></fA43><fA44><s0>0000</s0><s1>© 2007 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>45 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>07-0517249</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Journal of virology</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>Replication fidelity of RNA virus genomes is constrained by the opposing necessities of generating sufficient diversity for adaptation and maintaining genetic stability, but it is unclear how the largest viral RNA genomes have evolved and are maintained under these constraints. A coronavirus (CoV) nonstructural protein, nsp14, contains conserved active-site motifs of cellular exonucleases, including DNA proofreading enzymes, and the severe acute respiratory syndrome CoV (SARS-CoV) nsp14 has 3'-to-5' exoribonuclease (ExoN) activity in vitro. Here, we show that nsp14 ExoN remarkably increases replication fidelity of the CoV murine hepatitis virus (MHV). Replacement of conserved MHV ExoN active-site residues with alanines resulted in viable mutant viruses with growth and RNA synthesis defects that during passage accumulated 15-fold more mutations than wild-type virus without changes in growth fitness. The estimated mutation rate for ExoN mutants was similar to that reported for other RNA viruses, whereas that of wild-type MHV was less than the established rates for RNA viruses in general, suggesting that CoVs with intact ExoN replicate with unusually high fidelity. Our results indicate that nspl4 ExoN plays a critical role in prevention or repair of nucleotide incorporation errors during genome replication. The established mutants are unique tools to test the hypothesis that high replication fidelity is required for the evolution and stability of large RNA genomes.</s0></fC01><fC02 i1="01" i2="X"><s0>002A05C10</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Virus hépatite murine</s0><s2>NW</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Murine hepatitis virus</s0><s2>NW</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Murine hepatitis virus</s0><s2>NW</s2><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Réplication</s0><s5>05</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Replication</s0><s5>05</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Replicación</s0><s5>05</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Exoribonuclease</s0><s2>FE</s2><s5>06</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Exoribonuclease</s0><s2>FE</s2><s5>06</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Exoribonuclease</s0><s2>FE</s2><s5>06</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Mutation</s0><s5>07</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Mutation</s0><s5>07</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Mutación</s0><s5>07</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Virologie</s0><s5>08</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Virology</s0><s5>08</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Virología</s0><s5>08</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Coronavirus</s0><s2>NW</s2></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Coronavirus</s0><s2>NW</s2></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Coronavirus</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Esterases</s0><s2>FE</s2></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Esterases</s0><s2>FE</s2></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Esterases</s0><s2>FE</s2></fC07><fC07 i1="06" i2="X" l="FRE"><s0>Hydrolases</s0><s2>FE</s2></fC07><fC07 i1="06" i2="X" l="ENG"><s0>Hydrolases</s0><s2>FE</s2></fC07><fC07 i1="06" i2="X" l="SPA"><s0>Hydrolases</s0><s2>FE</s2></fC07><fC07 i1="07" i2="X" l="FRE"><s0>Enzyme</s0><s2>FE</s2></fC07><fC07 i1="07" i2="X" l="ENG"><s0>Enzyme</s0><s2>FE</s2></fC07><fC07 i1="07" i2="X" l="SPA"><s0>Enzima</s0><s2>FE</s2></fC07><fN21><s1>337</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/PascalFrancis/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000661 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PascalFrancis/Curation/biblio.hfd -nk 000661 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= SrasV1
|flux= PascalFrancis
|étape= Curation
|type= RBID
|clé= Pascal:07-0517249
|texte= High fidelity of murine hepatitis virus replication is decreased in nsp14 exoribonuclease mutants
}}
| This area was generated with Dilib version V0.6.33. |  |