ArticleAntimicrobial agents and chemotherapy2012
Impact of mutations at residue I223 of the neuraminidase protein on the resistance profile, replication level, and virulence of the 2009 pandemic influenza virus.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 67 citations in OpenAlex.
- Strain Matching of Seasonal Influenza Vaccines and Emergence of Neuraminidase Inhibitor Resistance in China from 2015 to 2025.Vaccines · 2026Article
- Molecular dynamics study on the effect of the N1 neuraminidase double mutant G147R/H274Y on oseltamivir sensitivity.RSC advances · 2024Article
- Influenza neuraminidase mutations and resistance to neuraminidase inhibitors.Emerging microbes & infections · 2024Review
- Increase of Synergistic Secondary Antiviral Mutations in the Evolution of A(H1N1)pdm09 Influenza Virus Neuraminidases.Viruses · 2024Article
- Low prevalence of influenza A strains with resistance markers in Brazil during 2017-2019 seasons.Frontiers in public health · 2022Article
- 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
- Development of A4 antibody for detection of neuraminidase I223R/H275Y-associated antiviral multidrug-resistant influenza virus.Nature communications · 2020Article
- Lack of selective resistance of influenza A virus in presence of host-targeted antiviral, UV-4B.Scientific reports · 2019Article
- Replacement of neuraminidase inhibitor-susceptible influenza A(H1N1) with resistant phenotype in 2008 and circulation of susceptible influenza A and B viruses during 2009-2013, South Africa.Influenza and other respiratory viruses · 2019Article
- Article
- Susceptibility of influenza A(H1N1)/pdm2009, seasonal A(H3N2) and B viruses to Oseltamivir in Guangdong, China between 2009 and 2014.Scientific reports · 2017Article
- Identification of influenza A nucleoprotein body domain residues essential for viral RNA expression expose antiviral target.Virology journal · 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
- Article
- Drug resistance in influenza A virus: the epidemiology and management.Infection and drug resistance · 2017Review
- Modelling the emergence of influenza drug resistance: The roles of surface proteins, the immune response and antiviral mechanisms.PloS one · 2017Article
- A Review of Clinical Influenza A and B Infections With Reduced Susceptibility to Both Oseltamivir and Zanamivir.Open forum infectious diseases · 2017Review
- Complexities in Ferret Influenza Virus Pathogenesis and Transmission Models.Microbiology and molecular biology reviews : MMBR · 2016Review
- Influenza A(H7N9) virus acquires resistance-related neuraminidase I222T substitution when infected mallards are exposed to low levels of oseltamivir in water.Antimicrobial agents and chemotherapy · 2015Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Amino acid substitutions at residue I223 of the neuraminidase (NA) protein have been identified in 2009 pandemic influenza (pH1N1) variants with altered susceptibilities to NA inhibitors (NAIs). We used reverse genetics and site-directed mutagenesis to generate the recombinant A/Québec/144147/09 pH1N1 wild-type virus (WT) and five (I223R, I223V, H275Y, I223V-H275Y, and I223R-H275Y) NA mutants. A fluorimetry-based assay was used to determine 50% inhibitory concentrations (IC(50)s) of oseltamivir, zanamivir, and peramivir. Replicative capacity was analyzed by viral yield assays in ST6GalI-MDCK cells. Infectivity and transmission of the WT, H275Y, and I223V-H275Y recombinant viruses were evaluated in ferrets. As expected, the H275Y mutation conferred resistance to oseltamivir (982-fold) and peramivir (661-fold) compared to the drug-susceptible recombinant WT. The single I223R mutant was associated with reduced susceptibility to oseltamivir (53-fold), zanamivir (7-fold) and peramivir (10-fold), whereas the I223V virus had reduced susceptibility to oseltamivir (6-fold) only. Interestingly, enhanced levels of resistance to oseltamivir and peramivir and reduced susceptibility to zanamivir (1,647-, 17,347-, and 16-fold increases in IC(50)s, respectively) were observed for the I223R-H275Y recombinant, while the I223V-H275Y mutant exhibited 1,733-, 2,707-, and 2-fold increases in respective IC(50)s. The I223R and I223V changes were associated with equivalent or higher viral titers in vitro compared to the recombinant WT. Infectivity and transmissibility in ferrets were comparable between the recombinant WT and the H275Y or I223V-H275Y recombinants. In conclusion, amino acid changes at residue I223 may alter the NAI susceptibilities of pH1N1 variants without compromising fitness. Consequently, I223R and I223V mutations, alone or with H275Y, need to be thoroughly monitored.
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