Determining the Mutation Bias of Favipiravir in Influenza Virus Using Next-Generation Sequencing
Identifieur interne : 000355 ( Main/Curation ); précédent : 000354; suivant : 000356Determining the Mutation Bias of Favipiravir in Influenza Virus Using Next-Generation Sequencing
Auteurs : Daniel H. Goldhill [Royaume-Uni] ; Pinky Langat [Royaume-Uni] ; Hongyao Xie [Royaume-Uni] ; Monica Galiano [Royaume-Uni] ; Shahjahan Miah [Royaume-Uni] ; Paul Kellam [Royaume-Uni] ; Maria Zambon [Royaume-Uni] ; Angie Lackenby [Royaume-Uni] ; Wendy S. Barclay [Royaume-Uni]Source :
- Journal of Virology [ 0022-538X ] ; 2019.
Descripteurs français
- KwdFr :
- MESH :
- génétique : Amorces ADN, Virus de la grippe A.
- pharmacologie : Amides, Pyrazines.
- Analyse de séquence d'ARN, Animaux, Cellules HEK293, Cellules rénales canines Madin-Darby, Chiens, Humains, Mutation, Séquençage nucléotidique à haut débit, Virus de la grippe A.
English descriptors
- KwdEn :
- Amides (pharmacology), Animals, Bias, DNA Primers (genetics), Dogs, HEK293 Cells, High-Throughput Nucleotide Sequencing (methods), Humans, Influenza A virus (drug effects), Influenza A virus (genetics), Madin Darby Canine Kidney Cells, Mutation, Pyrazines (pharmacology), Sequence Analysis, RNA, Whole Genome Sequencing.
- MESH :
- chemical , genetics : DNA Primers.
- chemical , pharmacology : Amides, Pyrazines.
- drug effects : Influenza A virus.
- genetics : Influenza A virus.
- methods : High-Throughput Nucleotide Sequencing.
- Animals, Bias, Dogs, HEK293 Cells, Humans, Madin Darby Canine Kidney Cells, Mutation, Sequence Analysis, RNA, Whole Genome Sequencing.
Abstract
New antiviral drugs are needed as a first line of defense in the event of a novel influenza pandemic. Favipiravir is a broad-spectrum antiviral which is effective against influenza. The exact mechanism of how favipiravir works to inhibit influenza is still unclear. We used next-generation sequencing (NGS) to demonstrate that favipiravir causes mutations in influenza RNA. The greater depth of NGS sequence information over traditional sequencing methods allowed us to precisely determine the bias of particular mutations caused by favipiravir. NGS can also be used in a standard diagnostic pipeline to show that favipiravir is acting on the virus by revealing the mutation bias pattern typical to the drug. Our work will aid in testing whether viruses are resistant to favipiravir and may help demonstrate the effect of favipiravir on viruses in a clinical setting. This will be important if favipiravir is used during a future influenza pandemic.
Url:
DOI: 10.1128/JVI.01217-18
PubMed: 30381482
PubMed Central: 6321902
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PMC:6321902Le document en format XML
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<term>DNA Primers (genetics)</term>
<term>Dogs</term>
<term>HEK293 Cells</term>
<term>High-Throughput Nucleotide Sequencing (methods)</term>
<term>Humans</term>
<term>Influenza A virus (drug effects)</term>
<term>Influenza A virus (genetics)</term>
<term>Madin Darby Canine Kidney Cells</term>
<term>Mutation</term>
<term>Pyrazines (pharmacology)</term>
<term>Sequence Analysis, RNA</term>
<term>Whole Genome Sequencing</term>
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<keywords scheme="KwdFr" xml:lang="fr"><term>Amides (pharmacologie)</term>
<term>Amorces ADN (génétique)</term>
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<term>Cellules HEK293</term>
<term>Cellules rénales canines Madin-Darby</term>
<term>Chiens</term>
<term>Humains</term>
<term>Mutation</term>
<term>Pyrazines (pharmacologie)</term>
<term>Séquençage nucléotidique à haut débit ()</term>
<term>Virus de la grippe A ()</term>
<term>Virus de la grippe A (génétique)</term>
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<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DNA Primers</term>
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<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Amides</term>
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<term>Pyrazines</term>
</keywords>
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<term>Bias</term>
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<term>Madin Darby Canine Kidney Cells</term>
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<term>Whole Genome Sequencing</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Analyse de séquence d'ARN</term>
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<term>Chiens</term>
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<front><div type="abstract" xml:lang="en"><p>New antiviral drugs are needed as a first line of defense in the event of a novel influenza pandemic. Favipiravir is a broad-spectrum antiviral which is effective against influenza. The exact mechanism of how favipiravir works to inhibit influenza is still unclear. We used next-generation sequencing (NGS) to demonstrate that favipiravir causes mutations in influenza RNA. The greater depth of NGS sequence information over traditional sequencing methods allowed us to precisely determine the bias of particular mutations caused by favipiravir. NGS can also be used in a standard diagnostic pipeline to show that favipiravir is acting on the virus by revealing the mutation bias pattern typical to the drug. Our work will aid in testing whether viruses are resistant to favipiravir and may help demonstrate the effect of favipiravir on viruses in a clinical setting. This will be important if favipiravir is used during a future influenza pandemic.</p>
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