ArticlePloS one2011
A computational-experimental approach identifies mutations that enhance surface expression of an oseltamivir-resistant influenza neuraminidase.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- Characterization of oseltamivir-resistant A(H5N1) clade 2.3.4.4b, genotype D1.1 variants identified in poultry farms of British Columbia, Canada.Emerging microbes & infections · 2026Article
- Antiviral susceptibility of clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses from humans in the United States, October 2024 to February 2025.Emerging microbes & infections · 2026Article
- Detection and characterization of antiviral-resistant viruses during the influenza season of 2024-25.Microbiology spectrum · 2026Article
- Multicountry Spread of Influenza A(H1N1)pdm09 Viruses with Reduced Oseltamivir Inhibition, May 2023-February 2024.Emerging infectious diseases · 2024Article
- Predicting Permissive Mutations That Improve the Fitness of A(H1N1)pdm09 Viruses Bearing the H275Y Neuraminidase Substitution.Journal of virology · 2022Article
- Identification of a Permissive Secondary Mutation That Restores the Enzymatic Activity of Oseltamivir Resistance Mutation H275Y.Journal of virology · 2022Article
- Article
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- Winning the Tug-of-War Between Effector Gene Design and Pathogen Evolution in Vector Population Replacement Strategies.Frontiers in genetics · 2019Review
- Comprehensive profiling of translation initiation in influenza virus infected cells.PLoS pathogens · 2019Article
- Characterization of Influenza B Virus Variants with Reduced Neuraminidase Inhibitor Susceptibility.Antimicrobial agents and chemotherapy · 2018Article
- Susceptibility of influenza A(H1N1)/pdm2009, seasonal A(H3N2) and B viruses to Oseltamivir in Guangdong, China between 2009 and 2014.Scientific reports · 2017Article
- Antiviral susceptibility profile of influenza A viruses; keep an eye on immunocompromised patients under prolonged treatment.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2017Article
- Epistasis in protein evolution.Protein science : a publication of the Protein Society · 2016Review
- Development and applications of single-cycle infectious influenza A virus (sciIAV).Virus research · 2016Review
- Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice.Journal of virology · 2015Article
- Oseltamivir-resistant influenza A(H1N1)pdm2009 strains found in Brazil are endowed with permissive mutations, which compensate the loss of fitness imposed by antiviral resistance.Memorias do Instituto Oswaldo Cruz · 2015Article
- Understanding the cross-resistance of oseltamivir to H1N1 and H5N1 influenza A neuraminidase mutations using multidimensional computational analyses.Drug design, development and therapy · 2015Article
- Biophysics of protein evolution and evolutionary protein biophysics.Journal of the Royal Society, Interface · 2014Article
- Epistatic interactions between neuraminidase mutations facilitated the emergence of the oseltamivir-resistant H1N1 influenza viruses.Nature communications · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The His274→Tyr (H274Y) oseltamivir (Tamiflu) resistance mutation causes a substantial decrease in the total levels of surface-expressed neuraminidase protein and activity in early isolates of human seasonal H1N1 influenza, and in the swine-origin pandemic H1N1. In seasonal H1N1, H274Y only became widespread after the occurrence of secondary mutations that counteracted this decrease. H274Y is currently rare in pandemic H1N1, and it remains unclear whether secondary mutations exist that might similarly counteract the decreased neuraminidase surface expression associated with this resistance mutation in pandemic H1N1. Here we investigate the possibility of predicting such secondary mutations. We first test the ability of several computational approaches to retrospectively identify the secondary mutations that enhanced levels of surface-expressed neuraminidase protein and activity in seasonal H1N1 shortly before the emergence of oseltamivir resistance. We then use the most successful computational approach to predict a set of candidate secondary mutations to the pandemic H1N1 neuraminidase. We experimentally screen these mutations, and find that several of them do indeed partially counteract the decrease in neuraminidase surface expression caused by H274Y. Two of the secondary mutations together restore surface-expressed neuraminidase activity to wildtype levels, and also eliminate the very slight decrease in viral growth in tissue-culture caused by H274Y. Our work therefore demonstrates a combined computational-experimental approach for identifying mutations that enhance neuraminidase surface expression, and describes several specific mutations with the potential to be of relevance to the spread of oseltamivir resistance in pandemic H1N1.
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