ArticlePloS one2012
I223R mutation in influenza A(H1N1)pdm09 neuraminidase confers reduced susceptibility to oseltamivir and zanamivir and enhanced resistance with H275Y.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 53 citations in OpenAlex.
- Strain Matching of Seasonal Influenza Vaccines and Emergence of Neuraminidase Inhibitor Resistance in China from 2015 to 2025.Vaccines · 2026Article
- Are we cultivating the perfect storm for a human avian influenza pandemic?Biological research · 2024Review
- Zanamivir and baloxavir combination to cure persistent influenza and coronavirus infections after hematopoietic stem cell transplant.International journal of antimicrobial agents · 2024Article
- Antivirals Targeting the Surface Glycoproteins of Influenza Virus: Mechanisms of Action and Resistance.Viruses · 2021Review
- In Vitro Characterization of Multidrug-Resistant Influenza A(H1N1)pdm09 Viruses Carrying a Dual Neuraminidase Mutation Isolated from Immunocompromised Patients.Pathogens (Basel, Switzerland) · 2020Article
- Site-directed M2 proton channel inhibitors enable synergistic combination therapy for rimantadine-resistant pandemic influenza.PLoS pathogens · 2020Article
- Morin Hydrate Inhibits Influenza Virus entry into Host Cells and Has Anti-inflammatory Effect in Influenza-infected Mice.Immune network · 2020Article
- Development of A4 antibody for detection of neuraminidase I223R/H275Y-associated antiviral multidrug-resistant influenza virus.Nature communications · 2020Article
- Evolutionary, genetic, structural characterization and its functional implications for the influenza A (H1N1) infection outbreak in India from 2009 to 2017.Scientific reports · 2019Article
- Lack of selective resistance of influenza A virus in presence of host-targeted antiviral, UV-4B.Scientific reports · 2019Article
- A comparison of RSV and influenza in vitro kinetic parameters reveals differences in infecting time.PloS one · 2018Article
- Identification of neuraminidase inhibitors against dual H274Y/I222R mutant strains.Scientific reports · 2017Article
- Susceptibility of influenza A(H1N1)/pdm2009, seasonal A(H3N2) and B viruses to Oseltamivir in Guangdong, China between 2009 and 2014.Scientific reports · 2017Article
- Development of oseltamivir and zanamivir resistance in influenza A(H1N1)pdm09 virus, Denmark, 2014.Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin · 2017Article
- A Review of Clinical Influenza A and B Infections With Reduced Susceptibility to Both Oseltamivir and Zanamivir.Open forum infectious diseases · 2017Review
- Microsecond Molecular Dynamics Simulations of Influenza Neuraminidase Suggest a Mechanism for the Increased Virulence of Stalk-Deletion Mutants.The journal of physical chemistry. B · 2016Article
- Avian Influenza A Viruses: Evolution and Zoonotic Infection.Seminars in respiratory and critical care medicine · 2016Review
- Genetic Characterization of Circulating 2015 A(H1N1)pdm09 Influenza Viruses from Eastern India.PloS one · 2016Article
- Virological characterization of influenza H1N1pdm09 in Vietnam, 2010-2013.Influenza and other respiratory viruses · 2015Article
- Temperature-Sensitive Mutants in the Influenza A Virus RNA Polymerase: Alterations in the PA Linker Reduce Nuclear Targeting of the PB1-PA Dimer and Result in Viral Attenuation.Journal of virology · 2015Article
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11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundResistance of pandemic A(H1N1)2009 (H1N1pdm09) virus to neuraminidase inhibitors (NAIs) has remained limited. A new mutation I223R in the neuraminidase (NA) of H1N1pdm09 virus has been reported along with H275Y in immunocompromised patients. The aim of this study was to determine the impact of I223R on oseltamivir and zanamivir susceptibility.
methodsThe NA enzymatic characteristics and susceptibility to NAIs of viruses harbouring the mutations I223R and H275Y alone or in combination were analyzed on viruses produced by reverse genetics and on clinical isolates collected from an immunocompromised patient with sustained influenza H1N1pdm09 virus shedding and treated by oseltamivir (days 0-15) and zanamivir (days 15-25 and 70-80).
resultsCompared with the wild type, the NA of recombinant viruses and clinical isolates with H275Y or I223R mutations had about two-fold reduced affinity for the substrate. The H275Y and I223R isolates showed decreased susceptibility to oseltamivir (246-fold) and oseltamivir and zanamivir (8.9- and 4.9-fold), respectively. Reverse genetics assays confirmed these results and further showed that the double mutation H275Y and I223R conferred enhanced levels of resistance to oseltamivir and zanamivir (6195- and 15.2-fold). In the patient, six days after initiation of oseltamivir therapy, the mutation H275Y conferring oseltamivir resistance and the I223R mutation were detected in the NA. Mutations were detected concomitantly from day 6-69 but molecular cloning did not show any variant harbouring both mutations. Despite cessation of NAI treatment, the mutation I223R persisted along with additional mutations in the NA and the hemagglutinin.
conclusionsReduced susceptibility to both oseltamivir and zanamivir was conferred by the I223R mutation which potentiated resistance to both NAIs when associated with the H275Y mutation in the NA. Concomitant emergence of the I223R and H275Y mutations under oseltamivir treatment underlines the importance of close monitoring of treated patients especially those immunocompromised.
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