Modelling the emergence of influenza drug resistance: The roles of surface proteins, the immune response and antiviral mechanisms
Identifieur interne : 000683 ( Main/Exploration ); précédent : 000682; suivant : 000684Modelling the emergence of influenza drug resistance: The roles of surface proteins, the immune response and antiviral mechanisms
Auteurs : Hana M. Dobrovolny [États-Unis, Canada] ; Catherine A. A. Beauchemin [Canada, Japon]Source :
- PLoS ONE [ 1932-6203 ] ; 2017.
Descripteurs français
- KwdFr :
- Antiviraux (pharmacologie), Antiviraux (usage thérapeutique), Aptitude génétique, Grippe humaine (immunologie), Grippe humaine (traitement médicamenteux), Grippe humaine (virologie), Humains, Modèles théoriques, Mutation (génétique), Protéines membranaires (métabolisme), Résistance virale aux médicaments (), Résistance virale aux médicaments (immunologie), Résultat thérapeutique.
- MESH :
- génétique : Mutation.
- immunologie : Grippe humaine, Résistance virale aux médicaments.
- métabolisme : Protéines membranaires.
- pharmacologie : Antiviraux.
- traitement médicamenteux : Grippe humaine.
- usage thérapeutique : Antiviraux.
- virologie : Grippe humaine.
- Aptitude génétique, Humains, Modèles théoriques, Résistance virale aux médicaments, Résultat thérapeutique.
English descriptors
- KwdEn :
- Antiviral Agents (pharmacology), Antiviral Agents (therapeutic use), Drug Resistance, Viral (drug effects), Drug Resistance, Viral (immunology), Genetic Fitness, Humans, Influenza, Human (drug therapy), Influenza, Human (immunology), Influenza, Human (virology), Membrane Proteins (metabolism), Models, Theoretical, Mutation (genetics), Treatment Outcome.
- MESH :
- chemical , metabolism : Membrane Proteins.
- chemical , pharmacology : Antiviral Agents.
- chemical , therapeutic use : Antiviral Agents.
- drug effects : Drug Resistance, Viral.
- drug therapy : Influenza, Human.
- genetics : Mutation.
- immunology : Drug Resistance, Viral, Influenza, Human.
- virology : Influenza, Human.
- Genetic Fitness, Humans, Models, Theoretical, Treatment Outcome.
Abstract
The emergence of influenza drug resistance has become of particular interest as current planning for an influenza pandemic involves using massive amounts of antiviral drugs. We use semi-stochastic simulations to examine the emergence of drug resistant mutants during the course of a single infection within a patient in the presence and absence of antiviral therapy. We specifically examine three factors and their effect on the emergence of drug-resistant mutants: antiviral mechanism, the immune response, and surface proteins. We find that adamantanes, because they act at the start of the replication cycle to prevent infection, are less likely to produce drug-resistant mutants than NAIs, which act at the end of the replication cycle. A mismatch between surface proteins and internal RNA results in drug-resistant mutants being less likely to emerge, and emerging later in the infection because the mismatch gives antivirals a second chance to prevent propagation of the mutation. The immune response subdues slow growing infections, further reducing the probability that a drug resistant mutant will emerge and yield a drug-resistant infection. These findings improve our understanding of the factors that contribute to the emergence of drug resistance during the course of a single influenza infection.
Url:
DOI: 10.1371/journal.pone.0180582
PubMed: 28700622
PubMed Central: 5503263
Affiliations:
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Le document en format XML
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We use semi-stochastic simulations to examine the emergence of drug resistant mutants during the course of a single infection within a patient in the presence and absence of antiviral therapy. We specifically examine three factors and their effect on the emergence of drug-resistant mutants: antiviral mechanism, the immune response, and surface proteins. We find that adamantanes, because they act at the start of the replication cycle to prevent infection, are less likely to produce drug-resistant mutants than NAIs, which act at the end of the replication cycle. A mismatch between surface proteins and internal RNA results in drug-resistant mutants being less likely to emerge, and emerging later in the infection because the mismatch gives antivirals a second chance to prevent propagation of the mutation. The immune response subdues slow growing infections, further reducing the probability that a drug resistant mutant will emerge and yield a drug-resistant infection. These findings improve our understanding of the factors that contribute to the emergence of drug resistance during the course of a single influenza infection.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Li, Tcm" uniqKey="Li T">TCM Li</name></author><author><name sortKey="Chan, Mcw" uniqKey="Chan M">MCW Chan</name></author><author><name sortKey="Lee, N" uniqKey="Lee N">N Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abed, Y" uniqKey="Abed Y">Y Abed</name></author><author><name sortKey="Goyette, N" uniqKey="Goyette N">N Goyette</name></author><author><name sortKey="Boivin, G" uniqKey="Boivin G">G Boivin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jefferson, T" uniqKey="Jefferson T">T Jefferson</name></author><author><name sortKey="Demicheli, V" uniqKey="Demicheli V">V Demicheli</name></author><author><name sortKey="Rivetti, D" uniqKey="Rivetti D">D 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Palmer</name></author><author><name sortKey="Dobrovolny, Hm" uniqKey="Dobrovolny H">HM Dobrovolny</name></author><author><name sortKey="Beauchemin, Caa" uniqKey="Beauchemin C">CAA Beauchemin</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Canada</li><li>Japon</li><li>États-Unis</li></country><region><li>Texas</li></region></list><tree><country name="États-Unis"><region name="Texas"><name sortKey="Dobrovolny, Hana M" sort="Dobrovolny, Hana M" uniqKey="Dobrovolny H" first="Hana M." last="Dobrovolny">Hana M. Dobrovolny</name></region></country><country name="Canada"><noRegion><name sortKey="Dobrovolny, Hana M" sort="Dobrovolny, Hana M" uniqKey="Dobrovolny H" first="Hana M." last="Dobrovolny">Hana M. Dobrovolny</name></noRegion><name sortKey="Beauchemin, Catherine A A" sort="Beauchemin, Catherine A A" uniqKey="Beauchemin C" first="Catherine A. A." last="Beauchemin">Catherine A. A. Beauchemin</name></country><country name="Japon"><noRegion><name sortKey="Beauchemin, Catherine A A" sort="Beauchemin, Catherine A A" uniqKey="Beauchemin C" first="Catherine A. A." last="Beauchemin">Catherine A. A. Beauchemin</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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