PandemieGrippaleV1, PubMed, Curation, bibRecord, 000451

Identification of influenza A nucleoprotein body domain residues essential for viral RNA expression expose antiviral target.

Identifieur interne : 000451 ( PubMed/Curation ); précédent : 000450; suivant : 000452

Identification of influenza A nucleoprotein body domain residues essential for viral RNA expression expose antiviral target.

Auteurs : Alicia M. Davis [États-Unis] ; Jose Ramirez [États-Unis] ; Laura L. Newcomb [États-Unis]

Source :

Virology journal [ 1743-422X ] ; 2017.

RBID : pubmed:28173821

Descripteurs français

English descriptors

KwdEn :
- Amino Acid Sequence, Amino Acid Substitution, Antiviral Agents (metabolism), Antiviral Agents (pharmacology), Gene Expression Regulation, Viral (physiology), HEK293 Cells, Humans, Influenza A virus (drug effects), Influenza A virus (genetics), Influenza A virus (metabolism), Influenza, Human (genetics), Influenza, Human (metabolism), Mutation, RNA, Viral (biosynthesis), RNA, Viral (drug effects), RNA, Viral (genetics), RNA-Binding Proteins (genetics), RNA-Binding Proteins (metabolism), Ribonucleoproteins (genetics), Ribonucleoproteins (metabolism), Structure-Activity Relationship, Transfection, Viral Core Proteins (genetics), Viral Core Proteins (metabolism), Viral Proteins (drug effects), Viral Proteins (genetics), Virus Replication.
MESH :
- chemical , biosynthesis : RNA, Viral.
- chemical , drug effects : RNA, Viral, Viral Proteins.
- chemical , genetics : RNA, Viral, RNA-Binding Proteins, Ribonucleoproteins, Viral Core Proteins, Viral Proteins.
- chemical , metabolism : Antiviral Agents, RNA-Binding Proteins, Ribonucleoproteins, Viral Core Proteins.
- chemical , pharmacology : Antiviral Agents.
- drug effects : Influenza A virus.
- genetics : Influenza A virus, Influenza, Human.
- metabolism : Influenza A virus, Influenza, Human.
- physiology : Gene Expression Regulation, Viral.
- Amino Acid Sequence, Amino Acid Substitution, HEK293 Cells, Humans, Mutation, Structure-Activity Relationship, Transfection, Virus Replication.

Abstract

Influenza A virus is controlled with yearly vaccination while emerging global pandemics are kept at bay with antiviral medications. Unfortunately, influenza A viruses have emerged resistance to approved influenza antivirals. Accordingly, there is an urgent need for novel antivirals to combat emerging influenza A viruses resistant to current treatments. Conserved viral proteins are ideal targets because conserved protein domains are present in most, if not all, influenza subtypes, and are presumed less prone to evolve viable resistant versions. The threat of an antiviral resistant influenza pandemic justifies our study to identify and characterize antiviral targets within influenza proteins that are highly conserved. Influenza A nucleoprotein (NP) is highly conserved and plays essential roles throughout the viral lifecycle, including viral RNA synthesis.

DOI: 10.1186/s12985-017-0694-8
PubMed: 28173821

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Le document en format XML

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<term>Amino Acid Substitution</term>
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<term>Antiviral Agents (pharmacology)</term>
<term>Gene Expression Regulation, Viral (physiology)</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Influenza A virus (drug effects)</term>
<term>Influenza A virus (genetics)</term>
<term>Influenza A virus (metabolism)</term>
<term>Influenza, Human (genetics)</term>
<term>Influenza, Human (metabolism)</term>
<term>Mutation</term>
<term>RNA, Viral (biosynthesis)</term>
<term>RNA, Viral (drug effects)</term>
<term>RNA, Viral (genetics)</term>
<term>RNA-Binding Proteins (genetics)</term>
<term>RNA-Binding Proteins (metabolism)</term>
<term>Ribonucleoproteins (genetics)</term>
<term>Ribonucleoproteins (metabolism)</term>
<term>Structure-Activity Relationship</term>
<term>Transfection</term>
<term>Viral Core Proteins (genetics)</term>
<term>Viral Core Proteins (metabolism)</term>
<term>Viral Proteins (drug effects)</term>
<term>Viral Proteins (genetics)</term>
<term>Virus Replication</term>
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<keywords scheme="KwdFr" xml:lang="fr"><term>ARN viral ()</term>
<term>ARN viral (biosynthèse)</term>
<term>ARN viral (génétique)</term>
<term>Antiviraux (métabolisme)</term>
<term>Antiviraux (pharmacologie)</term>
<term>Cellules HEK293</term>
<term>Grippe humaine (génétique)</term>
<term>Grippe humaine (métabolisme)</term>
<term>Humains</term>
<term>Mutation</term>
<term>Protéines de liaison à l'ARN (génétique)</term>
<term>Protéines de liaison à l'ARN (métabolisme)</term>
<term>Protéines du core viral (génétique)</term>
<term>Protéines du core viral (métabolisme)</term>
<term>Protéines virales ()</term>
<term>Protéines virales (génétique)</term>
<term>Relation structure-activité</term>
<term>Ribonucléoprotéines (génétique)</term>
<term>Ribonucléoprotéines (métabolisme)</term>
<term>Régulation de l'expression des gènes viraux (physiologie)</term>
<term>Réplication virale</term>
<term>Substitution d'acide aminé</term>
<term>Séquence d'acides aminés</term>
<term>Transfection</term>
<term>Virus de la grippe A ()</term>
<term>Virus de la grippe A (génétique)</term>
<term>Virus de la grippe A (métabolisme)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>RNA, Viral</term>
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<term>RNA-Binding Proteins</term>
<term>Ribonucleoproteins</term>
<term>Viral Core Proteins</term>
<term>Viral Proteins</term>
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<term>Protéines du core viral</term>
<term>Protéines virales</term>
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<term>Protéines du core viral</term>
<term>Ribonucléoprotéines</term>
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<term>Amino Acid Substitution</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Mutation</term>
<term>Structure-Activity Relationship</term>
<term>Transfection</term>
<term>Virus Replication</term>
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<term>Cellules HEK293</term>
<term>Humains</term>
<term>Mutation</term>
<term>Protéines virales</term>
<term>Relation structure-activité</term>
<term>Réplication virale</term>
<term>Substitution d'acide aminé</term>
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<front><div type="abstract" xml:lang="en">Influenza A virus is controlled with yearly vaccination while emerging global pandemics are kept at bay with antiviral medications. Unfortunately, influenza A viruses have emerged resistance to approved influenza antivirals. Accordingly, there is an urgent need for novel antivirals to combat emerging influenza A viruses resistant to current treatments. Conserved viral proteins are ideal targets because conserved protein domains are present in most, if not all, influenza subtypes, and are presumed less prone to evolve viable resistant versions. The threat of an antiviral resistant influenza pandemic justifies our study to identify and characterize antiviral targets within influenza proteins that are highly conserved. Influenza A nucleoprotein (NP) is highly conserved and plays essential roles throughout the viral lifecycle, including viral RNA synthesis.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28173821</PMID>
<DateCompleted><Year>2018</Year>
<Month>01</Month>
<Day>19</Day>
</DateCompleted>
<DateRevised><Year>2018</Year>
<Month>11</Month>
<Day>13</Day>
</DateRevised>
<Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1743-422X</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>14</Volume>
<Issue>1</Issue>
<PubDate><Year>2017</Year>
<Month>02</Month>
<Day>07</Day>
</PubDate>
</JournalIssue>
<Title>Virology journal</Title>
<ISOAbbreviation>Virol. J.</ISOAbbreviation>
</Journal>
<ArticleTitle>Identification of influenza A nucleoprotein body domain residues essential for viral RNA expression expose antiviral target.</ArticleTitle>
<Pagination><MedlinePgn>22</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1186/s12985-017-0694-8</ELocationID>
<Abstract><AbstractText Label="BACKGROUND">Influenza A virus is controlled with yearly vaccination while emerging global pandemics are kept at bay with antiviral medications. Unfortunately, influenza A viruses have emerged resistance to approved influenza antivirals. Accordingly, there is an urgent need for novel antivirals to combat emerging influenza A viruses resistant to current treatments. Conserved viral proteins are ideal targets because conserved protein domains are present in most, if not all, influenza subtypes, and are presumed less prone to evolve viable resistant versions. The threat of an antiviral resistant influenza pandemic justifies our study to identify and characterize antiviral targets within influenza proteins that are highly conserved. Influenza A nucleoprotein (NP) is highly conserved and plays essential roles throughout the viral lifecycle, including viral RNA synthesis.</AbstractText>
<AbstractText Label="METHODS">Using NP crystal structure, we targeted accessible amino acids for substitution. To characterize the NP proteins, reconstituted viral ribonucleoproteins (vRNPs) were expressed in 293 T cells, RNA was isolated, and reverse transcription - quantitative PCR (RT-qPCR) was employed to assess viral RNA expressed from reconstituted vRNPs. Location was confirmed using cellular fractionation and western blot, along with observation of NP-GFP fusion proteins. Nucleic acid binding, oligomerization, and vRNP formation, were each assessed with native gel electrophoresis.</AbstractText>
<AbstractText Label="RESULTS">Here we report characterization of an accessible and conserved five amino acid region within the NP body domain that plays a redundant but essential role in viral RNA synthesis. Our data demonstrate substitutions in this domain did not alter NP localization, oligomerization, or ability to bind nucleic acids, yet resulted in a defect in viral RNA expression. To define this region further, single and double amino acid substitutions were constructed and investigated. All NP single substitutions were functional, suggesting redundancy, yet different combinations of two amino acid substitutions resulted in a significant defect in RNA expression, confirming these accessible amino acids in the NP body domain play an important role in viral RNA synthesis.</AbstractText>
<AbstractText Label="CONCLUSIONS">The identified conserved and accessible NP body domain represents a viable antiviral target to counter influenza replication and this research will contribute to the well-informed design of novel therapies to combat emerging influenza viruses.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Davis</LastName>
<ForeName>Alicia M</ForeName>
<Initials>AM</Initials>
<AffiliationInfo><Affiliation>Department of Biology, California State University San Bernardino, San Bernardino, CA, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Present Address: Irell & Manella Graduate School of Biological Sciences, City of Hope, Duarte, CA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ramirez</LastName>
<ForeName>Jose</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department of Biology, California State University San Bernardino, San Bernardino, CA, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Present Address: Tufts University School of Medicine, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Newcomb</LastName>
<ForeName>Laura L</ForeName>
<Initials>LL</Initials>
<AffiliationInfo><Affiliation>Department of Biology, California State University San Bernardino, San Bernardino, CA, USA. lnewcomb@csusb.edu.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>R25 GM100829</GrantID>
<Acronym>GM</Acronym>
<Agency>NIGMS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>SC3 GM099559</GrantID>
<Acronym>GM</Acronym>
<Agency>NIGMS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>T34 GM083883</GrantID>
<Acronym>GM</Acronym>
<Agency>NIGMS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
</GrantList>
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</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2017</Year>
<Month>02</Month>
<Day>07</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>England</Country>
<MedlineTA>Virol J</MedlineTA>
<NlmUniqueID>101231645</NlmUniqueID>
<ISSNLinking>1743-422X</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C048842">NP protein, Influenza A virus</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D012367">RNA, Viral</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D016601">RNA-Binding Proteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D012261">Ribonucleoproteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014758">Viral Core Proteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014764">Viral Proteins</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000595" MajorTopicYN="N">Amino Acid Sequence</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D019943" MajorTopicYN="N">Amino Acid Substitution</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015967" MajorTopicYN="N">Gene Expression Regulation, Viral</DescriptorName>
<QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D057809" MajorTopicYN="N">HEK293 Cells</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009980" MajorTopicYN="N">Influenza A virus</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007251" MajorTopicYN="N">Influenza, Human</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009154" MajorTopicYN="N">Mutation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D012367" MajorTopicYN="N">RNA, Viral</DescriptorName>
<QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016601" MajorTopicYN="N">RNA-Binding Proteins</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D012261" MajorTopicYN="N">Ribonucleoproteins</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013329" MajorTopicYN="N">Structure-Activity Relationship</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014162" MajorTopicYN="N">Transfection</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014758" MajorTopicYN="N">Viral Core Proteins</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014764" MajorTopicYN="N">Viral Proteins</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014779" MajorTopicYN="N">Virus Replication</DescriptorName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Influenza</Keyword>
<Keyword MajorTopicYN="Y">Nucleoprotein</Keyword>
<Keyword MajorTopicYN="Y">RNA</Keyword>
<Keyword MajorTopicYN="Y">Virus</Keyword>
</KeywordList>
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<Month>09</Month>
<Day>09</Day>
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<PubMedPubDate PubStatus="accepted"><Year>2017</Year>
<Month>01</Month>
<Day>30</Day>
</PubMedPubDate>
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Identification of influenza A nucleoprotein body domain residues essential for viral RNA expression expose antiviral target.

Identification of influenza A nucleoprotein body domain residues essential for viral RNA expression expose antiviral target.

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