Abstract: Furthermore, E119D and E119D-H274Y mutants in the pH1N1 background maintained overall fitness properties in vitro and in vivo.
Abstract: Of the 14 single and double mutant viruses recovered in the backbone of pH1N1, four variants (E119D, E119A/D/G-H274Y) exhibited reduced inhibition by all of the NAIs and two variants (E119D and E119D-H274Y) retained the overall properties of gene stability, replicative efficiency, pathogenicity, and transmissibility in vitro and in vivo.
Abstract: Of the nine recombinant H5N1 viruses, four variants (E119D, E119A/D/G-
Oseltamivir-resistant influenza A (H1N1) virus strain with an H274Y mutation in neuraminidase persists without drug pressure in infected mallards.
PMID: 25616792
2015
Applied and environmental microbiology
Abstract: In this in vivo mallard (Anas platyrhynchos) study, we tested whether an OC-resistant avian IAV (H1N1) strain with an H274Y mutation in the neuraminidase (NA-H274Y) could retain resistance while drug pressure was gradually removed.
Competitive fitness of influenza B viruses with neuraminidase inhibitor-resistant substitutions in a coinfection model of the human airway epithelium.
Abstract: Based on the lack of attenuated replication of rg-E119A in NHBE cells in the presence of oseltamivir or zanamivir and the fitness advantage of rg-H274Y over rg-WT, we emphasize the importance of these substitutions in the NA glycoprotein.
Abstract: Human infections with influenza B viruses carrying the E119A or H274Y substitution could limit the therapeutic options for those infected; the emergence of such viruses should be closely monitored.
Abstract: The replication in NHBE cells of viruses with reduced inhibition by oseltamivir (recombinant virus with the E119A mutation generated by reverse genetics [rg-E119A], rg-D198E, rg-I222T, rg-
Influenza A viruses of swine circulating in the United States during 2009-2014 are susceptible to neuraminidase inhibitors but show lineage-dependent resistance to adamantanes.
Discussion: Our extensive screening of the NA IAV-S sequences identified one IAV-S sequence that possesses the H274Y-NA, a known maker of clinically relevant NAI resistance.
Discussion: The studies are needed to re-evaluate the I117V-NA marker, as well
Discussion: Two IAV-S with the H274Y-NA were reported from a farm in Canada, where humans were infected with a reassortant influenza A virus (HA/NA from human H1N1 and internal genes from swine TRIG IAV).
Molecular docking of potential inhibitors for influenza H7N9.
PMID: 25861376
2015
Computational and mathematical methods in medicine
Introduction: Furthermore, the authors proposed that the drug resistance caused by mutation of R294K in H7N9 was more serious than that caused by mutation of H274Y in H7N1.
Influenza A(H7N9) virus acquires resistance-related neuraminidase I222T substitution when infected mallards are exposed to low levels of oseltamivir in water.
PMID: 26077257
2015
Antimicrobial agents and chemotherapy
Discussion: NA I222T and several other amino acid substitutions at the 222 NA residue generate reduced sensitivity to NAIs, either as independent resistance substitutions or, perhaps of more concern, by enhancing resistance induced by H274Y in N1 virus or by E119V in N2 virus.
Discussion: Sequential evolution of permissive amino acids in a viral population over time, including at the NA 222 position, appears to facilitate acquisition and harboring of new resistance mutations, illustrated by the OC-resistant human seasonal A(H1N1)/H274Y virus that circulated in 2007 to 2009.
Discussion: Several substitutions also seem to restore reduced fitness: I222T/V/R
SNPer: an R library for quantitative variant analysis on single nucleotide polymorphisms among influenza virus populations.
Abstract: More minor genetic alterations in genetic drift can lead to influenza drug resistance such as the H274Y mutation associated with oseltamivir resistance.
Oseltamivir Resistance in Influenza A(H6N2) Caused by an R292K Substitution in Neuraminidase Is Not Maintained in Mallards without Drug Pressure.
Introduction: NAI resistance substitutions in poultry adapted avian IAVs, detected in treated humans, are also subtype-specific, with R292K or E119V most usual in H7N9 viruses and H274Y in H5N1 viruses.
Introduction: The H274Y NA substitution was induced in a Mallard H1N1 vir
Discussion: Among human IAVs, oseltamivir resistant H1N1/H274Y viruses with a suitable genetic context can circulate without drug pressure, but to date no circulation of resistant human H3N2 viruses has been seen.
Discussion: In avian IAVs, it was previously observed in vivo that an H1N1/H274Y virus, which had acquired resistance by OC exposure in Mallards, maintained the resistance substitution without drug pressure.
Study of oseltamivir and zanamivir resistance-related mutations in influenza viruses isolated from wild mallards in Sweden.
Method: The literature describing NAI resistance mutations has been reviewed, whereupon nine OC (V116A, I117V, E119V, D198N, I222V, H274Y, R292K, N
Discussion: For example, the OC resistance-related mutation H274Y (N2 numbering) in pandemic H1N1 A/Osaka/180/2009 resulted in IC50 of 93.9, 1,048.2 and 1,333.8 nM analyzed by CL, FL or CM assay respectively.
Discussion: In the case of H5N1 2.2 A/Turkey/15/06 recombinant virus and inhibition by OC the IC50 for E119A, H274Y and N294S were 236.5, 6308.0 and 424.2 nM respectively (FL assay).
IV mutation literature information.
PMID: 
2015
Veterinary research
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