Genetic microheterogeneity of emerging H275Y influenza virus A (H1N1) in Toronto, Ontario, Canada from the 2007–2008 respiratory season

Abstract Background The H275Y mutation (H274Y in N2 numbering) in the neuraminidase (NA) gene (segment 6) of the influenza virus A (H1N1) genome is linked to oseltamivir resistance. Objectives To determine the percentage of influenza virus A (H1N1) isolates that carry the H275Y mutation in the NA ge...

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Bibliographic Details
Published in:Journal of clinical virology 2009-06, Vol.45 (2), p.142-145
Main Authors: Eshaghi, A, Bolotin, S, Burton, L, Low, D.E, Mazzulli, T, Drews, S.J
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Allergy and Immunology
Amino Acid Substitution - genetics
Antiviral Agents - pharmacology
Biological and medical sciences
Child
Child, Preschool
Drug Resistance, Viral
Female
Fundamental and applied biological sciences. Psychology
Genetics
H275Y
Human viral diseases
Humans
Infant
Infectious Disease
Infectious diseases
Influenza
Influenza A virus
Influenza A Virus, H1N1 Subtype - genetics
Influenza A Virus, H1N1 Subtype - isolation & purification
Influenza, Human - epidemiology
Influenza, Human - virology
Male
Medical sciences
Microbiology
Middle Aged
Miscellaneous
Molecular Sequence Data
Mutation, Missense
Neuraminidase - genetics
Ontario - epidemiology
Oseltamivir
Oseltamivir - pharmacology
Polymorphism, Genetic
Pyrosequencing
Resistance
Sequence Analysis, DNA
Viral diseases
Viral Proteins - genetics
Virology
Young Adult
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Summary:Abstract Background The H275Y mutation (H274Y in N2 numbering) in the neuraminidase (NA) gene (segment 6) of the influenza virus A (H1N1) genome is linked to oseltamivir resistance. Objectives To determine the percentage of influenza virus A (H1N1) isolates that carry the H275Y mutation in the NA gene in Toronto, Ontario, Canada and to characterize select oseltamivir resistant and susceptible isolates using sequence analysis. Study design Sanger sequencing was used to determine strain type and H275Y mutations based on partial sequencing of the hemagglutinin (HA) (segment 4) and NA genes. Mutations in the NS1 gene (segment 8) were determined by Sanger sequencing and pyrosequencing. Statistical analysis of demographics and proportions of H275 and H275Y isolates with mutations was carried out using χ2 analyses. Results The HA gene of influenza virus A (H1N1) isolates collected during the 2007–2008 respiratory season was most like influenza A/Brisbane/59/2007, Clade 2, subclade B. Seventeen percent of these isolates possessed the H275Y NA mutation associated with oseltamivir resistance. H275Y isolates were more likely than H275 isolates to have the mutations A209T and R224G in NS1 ( χ2 = 284.9, df = 2, p < 0.0001). Conclusions During the 2007–2008 influenza season in Toronto, Ontario, Canada, 17% of influenza virus A (H1N1) isolates carried the H275Y mutation associated with oseltamivir resistance. These H275Y isolates were more likely than H275 isolates to exhibit unique microheterogeneity in the gene encoding the NS1 protein.
ISSN:1386-6532
1873-5967
DOI:10.1016/j.jcv.2009.04.010