MersV1, PubMed, Checkpoint, bibRecord, 000F68

Mutagenesis of S-Adenosyl-l-Methionine-Binding Residues in Coronavirus nsp14 N7-Methyltransferase Demonstrates Differing Requirements for Genome Translation and Resistance to Innate Immunity.

Identifieur interne : 000F68 ( PubMed/Checkpoint ); précédent : 000F67; suivant : 000F69

Mutagenesis of S-Adenosyl-l-Methionine-Binding Residues in Coronavirus nsp14 N7-Methyltransferase Demonstrates Differing Requirements for Genome Translation and Resistance to Innate Immunity.

Auteurs : James Brett Case [États-Unis] ; Alison W. Ashbrook [États-Unis] ; Terence S. Dermody [États-Unis] ; Mark R. Denison [États-Unis]

Source :

Journal of virology [ 1098-5514 ] ; 2016.

RBID : pubmed:27252528

Descripteurs français

KwdFr :
- ARN viral (génétique), ARN viral (métabolisme), Adémétionine (), Adémétionine (métabolisme), Analyse de mutations d'ADN, Animaux, Antiviraux (pharmacologie), Biosynthèse des protéines, Cellules cultivées, Coronavirus (enzymologie), Génome viral (physiologie), Humains, Immunité innée (immunologie), Immunomodulation, Interféron bêta (pharmacologie), Mutagenèse, Mutation (génétique), Protéines virales non structurales (), Protéines virales non structurales (génétique), Protéines virales non structurales (métabolisme), Réaction de polymérisation en chaine en temps réel, Réplication virale, Similitude de séquences d'acides aminés, Souris, Souris de lignée C57BL, Souris knockout, Séquence d'acides aminés, Tumeurs du cerveau (enzymologie), Tumeurs du cerveau (génétique), Tumeurs du cerveau (immunologie), Tumeurs du cerveau (virologie).
MESH :
- enzymologie : Coronavirus, Tumeurs du cerveau.
- génétique : ARN viral, Mutation, Protéines virales non structurales, Tumeurs du cerveau.
- immunologie : Immunité innée, Tumeurs du cerveau.
- métabolisme : ARN viral, Adémétionine, Protéines virales non structurales.
- pharmacologie : Antiviraux, Interféron bêta.
- physiologie : Génome viral.
- virologie : Tumeurs du cerveau.
- Adémétionine, Analyse de mutations d'ADN, Animaux, Biosynthèse des protéines, Cellules cultivées, Humains, Immunomodulation, Mutagenèse, Protéines virales non structurales, Réaction de polymérisation en chaine en temps réel, Réplication virale, Similitude de séquences d'acides aminés, Souris, Souris de lignée C57BL, Souris knockout, Séquence d'acides aminés.

English descriptors

KwdEn :
- Amino Acid Sequence, Animals, Antiviral Agents (pharmacology), Brain Neoplasms (enzymology), Brain Neoplasms (genetics), Brain Neoplasms (immunology), Brain Neoplasms (virology), Cells, Cultured, Coronavirus (enzymology), DNA Mutational Analysis, Genome, Viral (physiology), Humans, Immunity, Innate (immunology), Immunomodulation, Interferon-beta (pharmacology), Mice, Mice, Inbred C57BL, Mice, Knockout, Mutagenesis, Mutation (genetics), Protein Biosynthesis, RNA, Viral (genetics), RNA, Viral (metabolism), Real-Time Polymerase Chain Reaction, S-Adenosylmethionine (chemistry), S-Adenosylmethionine (metabolism), Sequence Homology, Amino Acid, Viral Nonstructural Proteins (chemistry), Viral Nonstructural Proteins (genetics), Viral Nonstructural Proteins (metabolism), Virus Replication.
MESH :
- chemical , chemistry : S-Adenosylmethionine, Viral Nonstructural Proteins.
- chemical , genetics : RNA, Viral, Viral Nonstructural Proteins.
- chemical , metabolism : RNA, Viral, S-Adenosylmethionine, Viral Nonstructural Proteins.
- chemical , pharmacology : Antiviral Agents, Interferon-beta.
- enzymology : Brain Neoplasms, Coronavirus.
- genetics : Brain Neoplasms, Mutation.
- immunology : Brain Neoplasms, Immunity, Innate.
- physiology : Genome, Viral.
- virology : Brain Neoplasms.
- Amino Acid Sequence, Animals, Cells, Cultured, DNA Mutational Analysis, Humans, Immunomodulation, Mice, Mice, Inbred C57BL, Mice, Knockout, Mutagenesis, Protein Biosynthesis, Real-Time Polymerase Chain Reaction, Sequence Homology, Amino Acid, Virus Replication.

Abstract

Eukaryotic mRNAs possess a methylated 5'-guanosine cap that is required for RNA stability, efficient translation, and protection from cell-intrinsic defenses. Many viruses use 5' caps or other mechanisms to mimic a cap structure to limit detection of viral RNAs by intracellular innate sensors and to direct efficient translation of viral proteins. The coronavirus (CoV) nonstructural protein 14 (nsp14) is a multifunctional protein with N7-methyltransferase (N7-MTase) activity. The highly conserved S-adenosyl-l-methionine (SAM)-binding residues of the DxG motif are required for nsp14 N7-MTase activity in vitro However, the requirement for CoV N7-MTase activity and the importance of the SAM-binding residues during viral replication have not been determined. Here, we engineered mutations in murine hepatitis virus (MHV) nsp14 N7-MTase at residues D330 and G332 and determined the effects of these mutations on viral replication, sensitivity to mutagen, inhibition by type I interferon (IFN), and translation efficiency. Virus encoding a G332A substitution in nsp14 displayed delayed replication kinetics and decreased peak titers relative to wild-type (WT) MHV. In addition, replication of nsp14 G332A virus was diminished following treatment of cells with IFN-β, and nsp14 G332A genomes were translated less efficiently both in vitro and during viral infection. In contrast, substitution of alanine at MHV nsp14 D330 did not affect viral replication, sensitivity to mutagen, or inhibition by IFN-β compared to WT MHV. Our results demonstrate that the conserved MHV N7-MTase SAM-binding-site residues are not required for MHV viability and suggest that the determinants of CoV N7-MTase activity differ in vitro and during virus infection.

DOI: 10.1128/JVI.00542-16
PubMed: 27252528

Affiliations:

Links toward previous steps (curation, corpus...)

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Le document en format XML

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<term>Brain Neoplasms (genetics)</term>
<term>Brain Neoplasms (immunology)</term>
<term>Brain Neoplasms (virology)</term>
<term>Cells, Cultured</term>
<term>Coronavirus (enzymology)</term>
<term>DNA Mutational Analysis</term>
<term>Genome, Viral (physiology)</term>
<term>Humans</term>
<term>Immunity, Innate (immunology)</term>
<term>Immunomodulation</term>
<term>Interferon-beta (pharmacology)</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Knockout</term>
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<term>Mutation (genetics)</term>
<term>Protein Biosynthesis</term>
<term>RNA, Viral (genetics)</term>
<term>RNA, Viral (metabolism)</term>
<term>Real-Time Polymerase Chain Reaction</term>
<term>S-Adenosylmethionine (chemistry)</term>
<term>S-Adenosylmethionine (metabolism)</term>
<term>Sequence Homology, Amino Acid</term>
<term>Viral Nonstructural Proteins (chemistry)</term>
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<term>Analyse de mutations d'ADN</term>
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<term>Biosynthèse des protéines</term>
<term>Cellules cultivées</term>
<term>Coronavirus (enzymologie)</term>
<term>Génome viral (physiologie)</term>
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<term>Immunité innée (immunologie)</term>
<term>Immunomodulation</term>
<term>Interféron bêta (pharmacologie)</term>
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<term>Mutation (génétique)</term>
<term>Protéines virales non structurales ()</term>
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<term>Similitude de séquences d'acides aminés</term>
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<term>Souris de lignée C57BL</term>
<term>Souris knockout</term>
<term>Séquence d'acides aminés</term>
<term>Tumeurs du cerveau (enzymologie)</term>
<term>Tumeurs du cerveau (génétique)</term>
<term>Tumeurs du cerveau (immunologie)</term>
<term>Tumeurs du cerveau (virologie)</term>
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<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>S-Adenosylmethionine</term>
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<term>Interferon-beta</term>
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<term>Coronavirus</term>
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<term>Protéines virales non structurales</term>
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<term>DNA Mutational Analysis</term>
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<term>Immunomodulation</term>
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<term>Cellules cultivées</term>
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<front><div type="abstract" xml:lang="en">Eukaryotic mRNAs possess a methylated 5'-guanosine cap that is required for RNA stability, efficient translation, and protection from cell-intrinsic defenses. Many viruses use 5' caps or other mechanisms to mimic a cap structure to limit detection of viral RNAs by intracellular innate sensors and to direct efficient translation of viral proteins. The coronavirus (CoV) nonstructural protein 14 (nsp14) is a multifunctional protein with N7-methyltransferase (N7-MTase) activity. The highly conserved S-adenosyl-l-methionine (SAM)-binding residues of the DxG motif are required for nsp14 N7-MTase activity in vitro However, the requirement for CoV N7-MTase activity and the importance of the SAM-binding residues during viral replication have not been determined. Here, we engineered mutations in murine hepatitis virus (MHV) nsp14 N7-MTase at residues D330 and G332 and determined the effects of these mutations on viral replication, sensitivity to mutagen, inhibition by type I interferon (IFN), and translation efficiency. Virus encoding a G332A substitution in nsp14 displayed delayed replication kinetics and decreased peak titers relative to wild-type (WT) MHV. In addition, replication of nsp14 G332A virus was diminished following treatment of cells with IFN-β, and nsp14 G332A genomes were translated less efficiently both in vitro and during viral infection. In contrast, substitution of alanine at MHV nsp14 D330 did not affect viral replication, sensitivity to mutagen, or inhibition by IFN-β compared to WT MHV. Our results demonstrate that the conserved MHV N7-MTase SAM-binding-site residues are not required for MHV viability and suggest that the determinants of CoV N7-MTase activity differ in vitro and during virus infection.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27252528</PMID>
<DateCompleted><Year>2017</Year>
<Month>05</Month>
<Day>15</Day>
</DateCompleted>
<DateRevised><Year>2018</Year>
<Month>11</Month>
<Day>13</Day>
</DateRevised>
<Article PubModel="Electronic-Print"><Journal><ISSN IssnType="Electronic">1098-5514</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>90</Volume>
<Issue>16</Issue>
<PubDate><Year>2016</Year>
<Month>08</Month>
<Day>15</Day>
</PubDate>
</JournalIssue>
<Title>Journal of virology</Title>
<ISOAbbreviation>J. Virol.</ISOAbbreviation>
</Journal>
<ArticleTitle>Mutagenesis of S-Adenosyl-l-Methionine-Binding Residues in Coronavirus nsp14 N7-Methyltransferase Demonstrates Differing Requirements for Genome Translation and Resistance to Innate Immunity.</ArticleTitle>
<Pagination><MedlinePgn>7248-7256</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1128/JVI.00542-16</ELocationID>
<Abstract><AbstractText Label="UNLABELLED">Eukaryotic mRNAs possess a methylated 5'-guanosine cap that is required for RNA stability, efficient translation, and protection from cell-intrinsic defenses. Many viruses use 5' caps or other mechanisms to mimic a cap structure to limit detection of viral RNAs by intracellular innate sensors and to direct efficient translation of viral proteins. The coronavirus (CoV) nonstructural protein 14 (nsp14) is a multifunctional protein with N7-methyltransferase (N7-MTase) activity. The highly conserved S-adenosyl-l-methionine (SAM)-binding residues of the DxG motif are required for nsp14 N7-MTase activity in vitro However, the requirement for CoV N7-MTase activity and the importance of the SAM-binding residues during viral replication have not been determined. Here, we engineered mutations in murine hepatitis virus (MHV) nsp14 N7-MTase at residues D330 and G332 and determined the effects of these mutations on viral replication, sensitivity to mutagen, inhibition by type I interferon (IFN), and translation efficiency. Virus encoding a G332A substitution in nsp14 displayed delayed replication kinetics and decreased peak titers relative to wild-type (WT) MHV. In addition, replication of nsp14 G332A virus was diminished following treatment of cells with IFN-β, and nsp14 G332A genomes were translated less efficiently both in vitro and during viral infection. In contrast, substitution of alanine at MHV nsp14 D330 did not affect viral replication, sensitivity to mutagen, or inhibition by IFN-β compared to WT MHV. Our results demonstrate that the conserved MHV N7-MTase SAM-binding-site residues are not required for MHV viability and suggest that the determinants of CoV N7-MTase activity differ in vitro and during virus infection.</AbstractText>
<AbstractText Label="IMPORTANCE">Human coronaviruses, most notably severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, cause severe and lethal human disease. Since specific antiviral therapies are not available for the treatment of human coronavirus infections, it is essential to understand the functions of conserved CoV proteins in viral replication. Here, we show that substitution of alanine at G332 in the N7-MTase domain of nsp14 impairs viral replication, enhances sensitivity to the innate immune response, and reduces viral RNA translation efficiency. Our data support the idea that coronavirus RNA capping could be targeted for development of antiviral therapeutics.</AbstractText>
<CopyrightInformation>Copyright © 2016, American Society for Microbiology. All Rights Reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Case</LastName>
<ForeName>James Brett</ForeName>
<Initials>JB</Initials>
<AffiliationInfo><Affiliation>Departments of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ashbrook</LastName>
<ForeName>Alison W</ForeName>
<Initials>AW</Initials>
<AffiliationInfo><Affiliation>Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Dermody</LastName>
<ForeName>Terence S</ForeName>
<Initials>TS</Initials>
<AffiliationInfo><Affiliation>Departments of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Denison</LastName>
<ForeName>Mark R</ForeName>
<Initials>MR</Initials>
<AffiliationInfo><Affiliation>Departments of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA mark.denison@vanderbilt.edu.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>R01 AI108197</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 AI038296</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>T32 HL007751</GrantID>
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<ArticleIdList><ArticleId IdType="pubmed">27252528</ArticleId>
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<ReferenceList><Reference><Citation>Nat Immunol. 2011 Feb;12 (2):137-43</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21217758</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS Pathog. 2010 May 06;6(5):e1000896</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20463816</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Mol Biol. 2003 Aug 29;331(5):991-1004</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12927536</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Rev Immunol. 2002 Sep;2(9):675-87</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12209136</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2014 May;88(10):5319-27</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24623413</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Proc Natl Acad Sci U S A. 2015 Jul 28;112(30):9436-41</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26159422</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Rev Mol Cell Biol. 2004 Oct;5(10):827-35</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15459663</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2007 Nov;81(22):12135-44</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17804504</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5108-13</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16549795</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS Pathog. 2011 May;7(5):e1002059</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21637813</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS Pathog. 2013;9(10):e1003663</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24098121</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nucleic Acids Res. 1977 Dec;4(12):4133-49</Citation>
<ArticleIdList><ArticleId IdType="pubmed">600792</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS Pathog. 2013 Aug;9(8):e1003565</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23966862</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS Pathog. 2010 Apr 22;6(4):e1000863</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20421945</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell. 1976 Dec;9(4 PT 2):645-53</Citation>
<ArticleIdList><ArticleId IdType="pubmed">1017010</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Rev Microbiol. 2011 Dec 05;10 (1):51-65</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22138959</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Rev Immunol. 2013 Jan;13(1):46-57</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23237964</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2014 Apr;88(8):4251-64</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24478444</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Prog Nucleic Acid Res Mol Biol. 1979;22:327-53</Citation>
<ArticleIdList><ArticleId IdType="pubmed">523634</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2015 Jun;89(12):6418-26</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25855750</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2008 Aug;82(16):8071-84</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18417574</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2007 Jul;81(13):7189-99</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17459917</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2005 Nov;79(21):13373-84</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16227259</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell. 1975 Apr;4(4):379-86</Citation>
<ArticleIdList><ArticleId IdType="pubmed">164293</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2004 Jun;78(11):5619-32</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15140959</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell. 1997 Jun 13;89(6):951-61</Citation>
<ArticleIdList><ArticleId IdType="pubmed">9200613</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell. 2003 Jun 13;113(6):701-2</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12809601</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2002 Nov;76(21):11065-78</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12368349</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 1981 May;38(2):661-70</Citation>
<ArticleIdList><ArticleId IdType="pubmed">6165837</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 1982 Feb;41(2):557-65</Citation>
<ArticleIdList><ArticleId IdType="pubmed">6281467</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nucleic Acids Res. 2015 Sep 30;43(17):8416-34</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26304538</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Annu Rev Immunol. 2014;32:513-45</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24555472</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 1996 Jun;70(6):3947-60</Citation>
<ArticleIdList><ArticleId IdType="pubmed">8648732</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nature. 2010 Nov 18;468(7322):452-6</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21085181</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2013 Jun;87(11):6296-305</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23536667</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3484-9</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19208801</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Adv Virus Res. 2006;66:193-292</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16877062</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Proc Natl Acad Sci U S A. 1976 May;73(5):1559-63</Citation>
<ArticleIdList><ArticleId IdType="pubmed">1064023</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS Pathog. 2011 Oct;7(10):e1002294</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22022266</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Adv Virus Res. 2000;55:135-84</Citation>
<ArticleIdList><ArticleId IdType="pubmed">11050942</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
</PubmedData>
</pubmed>
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   |texte=   Mutagenesis of S-Adenosyl-l-Methionine-Binding Residues in Coronavirus nsp14 N7-Methyltransferase Demonstrates Differing Requirements for Genome Translation and Resistance to Innate Immunity.
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Mutagenesis of S-Adenosyl-l-Methionine-Binding Residues in Coronavirus nsp14 N7-Methyltransferase Demonstrates Differing Requirements for Genome Translation and Resistance to Innate Immunity.

Mutagenesis of S-Adenosyl-l-Methionine-Binding Residues in Coronavirus nsp14 N7-Methyltransferase Demonstrates Differing Requirements for Genome Translation and Resistance to Innate Immunity.

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