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Modelling the emergence of influenza drug resistance: The roles of surface proteins, the immune response and antiviral mechanisms

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...

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Autores principales: Dobrovolny, Hana M., Beauchemin, Catherine A. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503263/
https://www.ncbi.nlm.nih.gov/pubmed/28700622
http://dx.doi.org/10.1371/journal.pone.0180582
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author Dobrovolny, Hana M.
Beauchemin, Catherine A. A.
author_facet Dobrovolny, Hana M.
Beauchemin, Catherine A. A.
author_sort Dobrovolny, Hana M.
collection PubMed
description 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.
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spelling pubmed-55032632017-07-25 Modelling the emergence of influenza drug resistance: The roles of surface proteins, the immune response and antiviral mechanisms Dobrovolny, Hana M. Beauchemin, Catherine A. A. PLoS One Research Article 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. Public Library of Science 2017-07-10 /pmc/articles/PMC5503263/ /pubmed/28700622 http://dx.doi.org/10.1371/journal.pone.0180582 Text en © 2017 Dobrovolny, Beauchemin http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Dobrovolny, Hana M.
Beauchemin, Catherine A. A.
Modelling the emergence of influenza drug resistance: The roles of surface proteins, the immune response and antiviral mechanisms
title Modelling the emergence of influenza drug resistance: The roles of surface proteins, the immune response and antiviral mechanisms
title_full Modelling the emergence of influenza drug resistance: The roles of surface proteins, the immune response and antiviral mechanisms
title_fullStr Modelling the emergence of influenza drug resistance: The roles of surface proteins, the immune response and antiviral mechanisms
title_full_unstemmed Modelling the emergence of influenza drug resistance: The roles of surface proteins, the immune response and antiviral mechanisms
title_short Modelling the emergence of influenza drug resistance: The roles of surface proteins, the immune response and antiviral mechanisms
title_sort modelling the emergence of influenza drug resistance: the roles of surface proteins, the immune response and antiviral mechanisms
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503263/
https://www.ncbi.nlm.nih.gov/pubmed/28700622
http://dx.doi.org/10.1371/journal.pone.0180582
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