Genetic characterization of seasonal influenza A (H3N2) viruses in Ontario during 2010–2011 influenza season: high prevalence of mutations at antigenic sites |
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Authors: | AliReza Eshaghi Venkata R. Duvvuri Aimin Li Samir N. Patel Nathalie Bastien Yan Li Donald E. Low Jonathan B. Gubbay |
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Affiliation: | 1. Ontario Agency for Health Protection and Promotion, , Toronto, ON, Canada;2. Mount Sinai Hospital, , Toronto, ON, Canada;3. Centre for Disease Modelling, York University, , Toronto, ON, Canada;4. University of Toronto, , Toronto, ON, Canada;5. National Microbiology Laboratory, Public Health Agency of Canada, , Winnipeg, MB, Canada;6. The Hospital for Sick Children, , Toronto, ON, Canada |
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Abstract: | BackgroundThe direct effect of antigenic site mutations in influenza viruses on antigenic drift and vaccine effectiveness is poorly understood.ObjectiveTo investigate the genetic and antigenic characteristics of human influenza A (H3N2) viruses circulating in Ontario during the early 2010–2011 winter season.Study designWe sequenced the hemagglutinin (HA) and neuraminidase (NA) genes from 41 A(H3N2) viruses detected in nasopharyngeal specimens. Strain typing was performed by hemagglutination inhibition (HI) assay. Molecular and phylogenetic tree analyses were conducted.ResultsHA and NA genes showed high similarity to the 2010–2011 vaccine strain, A/Perth/16/2009 (H3N2)-like virus (97·7–98·5% and 98·7–99·5% amino acid (AA) identity, respectively). Compared to A/Perth/16/2009 strain, HA gene mutations were documented at 28 different AA positions across all five H3 antigenic sites, with a range of 5–11 mutations in individual viruses. Thirty-six (88%) viruses had 8 AA substitutions in common; none of these had reduced HI titer. Among Ontario isolates, 11 antigenic site AAs were positively selected with an increase in glycosylation sites.ConclusionThe presence of antigenic site mutations with high frequency among 2010–2011 influenza H3N2 isolates confirms ongoing adaptive H3N2 evolution. These may represent early phylogenetic changes that could cause antigenic drift with further mutations. Clinical relevance of antigenic site mutations not causing drift in HI assays is unknown and requires further investigation. In addition, viral sequencing information will assist with vaccine strain planning and may facilitate early detection of vaccine escape. |
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Keywords: | Antigenic site mutations genetic and antigenic characterization phylogenetic analysis positive selection analysis seasonal influenza A (H3N2) virus |
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