IV mutation literature information.


  Development and implementation of influenza a virus subtyping and detection of genotypic resistance to neuraminidase inhibitors.
 PMID: 20336728       2010       Journal of medical virology
Abstract: In the course of implementing the method, two H1N1 isolates with the H274Y mutation in the neuraminidase segment have been detected and their molecular features analyzed.


  First case in Italy of acquired resistance to oseltamivir in an immunocompromised patient with influenza A/H1N1v infection.
 PMID: 20447860       2010       Journal of clinical virology
Abstract: A pandemic influenza A/H1N1v strain with the neuraminidase H274Y mutation was detected in nasal secretions of a 2-year-old leukemic patient with influenza-like illness after 18 days of treatment with oseltamivir.


  Oseltamivir-resistant pandemic (H1N1)2009 in Yemen - case report.
 PMID: 20459681       2010       Virology journal
Abstract: Both clinical specimens presented the mutation S31N in the M2 gene associated with resistance to adamantanes and H274Y in NA gene associated with resistance to oseltamivir.
Conclusion: Both clinical specimens contained the mutation H274Y in NA gene associated with resistance to oseltamivir.
Discussion: H274Y jumped from clade2C (Hong Kong/2562/2006-like) to clade 1 (New Caledonia/20/1999-like) to clade 2B (Brisbane/59/2007-like) which included multiple introductions.


  Effect of neuraminidase inhibitor-resistant mutations on pathogenicity of clade 2.2 A/Turkey/15/06 (H5N1) influenza virus in ferrets.
 PMID: 20523902       2010       PLoS pathogens
Abstract: We generated seven genetically stable recombinant clade 2.2 A/Turkey/15/06-like (H5N1) influenza viruses carrying NA mutations located either in the framework residues (E119A, H274Y, N294S) or in close proximity to the NA enzyme active site (<
Table: H274Y
Discussion: Of 11 NA mutations studied, seven located within (E119A, H274Y, and N294S) or near (V116A, I117V, K150N, and Y252H) the enzyme active site were stably maintained and grew to titers comparable to WT virus in MDCK cells.


  Assessing the viral fitness of oseltamivir-resistant influenza viruses in ferrets, using a competitive-mixtures model.
 PMID: 20631138       2010       Journal of virology
Abstract: The competitive-mixtures model was also used to investigate the fitness of the seasonal A(H1N1) oseltamivir-resistant H274Y mutant and showed that within infected ferrets the H274Y mutant virus was marginally outgrown by the wild-type strain but demonstrated equivalent transmissibility between ferrets.


  Oseltamivir-resistant pandemic A/H1N1 virus is as virulent as its wild-type counterpart in mice and ferrets.
 PMID: 20661429       2010       PLoS pathogens
Abstract: A more important perivascular (day 6) and pleural (days 6 and 12) inflammation was noted in the lungs of mice infected with the H274Y mutant, which correlated with increased pulmonary levels of IL-6 and KC.
Abstract: Furthermore, the H274Y mutant strain was transmitted to ferrets.
Abstract: In conclusion, viral fitness of the H274Y pH1N1 isolate is not substantially altered and has the potential to induce severe disease and to disseminate.


  Dynamic residue interaction network analysis of the oseltamivir binding site of N1 neuraminidase and its H274Y mutation site conferring drug resistance in influenza A virus.
 PMID: 20668122       2010       Journal of clinical microbiology
Abstract: A C-to-T transition mutation in the neuraminidase gene from seasonal A/H1N1 causes a His-to-Tyr mutation at amino acid position 275 (H274Y, universal N2 numbering), conferring resistance against oseltamivir (Tamiflu).
Abstract: In samples with mixed populations, it can reliably detect as little as a 1% wild-type or 0.1% H274Y component.
Abstract: Optimization of primers and assay conditions produced a limit of detection of 100 gene copies per reaction for both wild-type and H274Y genotypes.


  [Drug-resistant influenza viruses: an overview].
 PMID: 20845746       2010       Nihon rinsho. Japanese journal of clinical medicine
Abstract: Between 2007 and early 2009, the prevalence of oseltamivir-resistant seasonal H1N1 variants that possess the His274Tyr neuraminidase mutation had dramatically increased, raising concerns regarding the utility of oseltamivir.


  Aurintricarboxylic acid inhibits influenza virus neuraminidase.
 PMID: 19014974       2009       Antiviral research
Abstract: ATA was equally potent in inhibiting the NA activity derived from wild-type NA and its H274Y mutant which renders NA resistance to inhibition by oseltamivir.
Result: ATA inhibited the wild-type NA and H274Y oseltamivir-resistant NA.
Result: In our assay, the H274Y mutation in NA of the H1N1 and H5N1 subtypes, i.e., NAH274Y(WSN)and NAH274(H5N1), resulted in resistance to oseltamivir carboxylate (GS4071), the active ingredient of oseltamivir, as indicated by a 191- and 885-fold increase in the IC50 values, respectively (not shown).


  Dynamic residue interaction network analysis of the oseltamivir binding site of N1 neuraminidase and its H274Y mutation site conferring drug resistance in influenza A virus.
 PMID: 19015327       2009       Antimicrobial agents and chemotherapy
Abstract: A-322278 decreased mortality rates and lung virus titers significantly more than oseltamivir in mice infected with the NA H274Y mutant when therapy was started 4 h before or even 48 h after infection.
Abstract: The new oral neuraminidase (NA) inhibitor A-322278 was evaluated in mice infected with influenza A/H1N1 wild-type virus or the oseltamivir-resistant (H274Y mutant) virus.



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