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Phylogenetic analysis of human influenza A/H3N2 viruses isolated in 2015 in Germany indicates significant genetic divergence from vaccine strains

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Abstract

Infections by H3N2-type influenza A viruses (IAV) resulted in significant numbers of hospitalization in several countries in 2014-2015, causing disease also in vaccinated individuals and, in some cases, fatal outcomes. In this study, sequence analysis of H3N2 viruses isolated in Germany from 1998 to 2015, including eleven H3N2 isolates collected early in 2015, was performed. Compared to the vaccine strain A/Texas/50/2012 (H3N2), the 2015 strains from Germany showed up to 4.5 % sequence diversity in their HA1 protein, indicating substantial genetic drift. The data further suggest that two distinct phylogroups, 3C.2 and 3C.3, with 1.6-2.3 % and 0.3-2.4 % HA1 nucleotide and amino acid sequence diversity, respectively, co-circulated in Germany in the 2014/2015 season. Distinct glycosylation patterns and amino acid substitutions in the hemagglutinin and neuraminidase proteins were identified, possibly contributing to the unusually high number of H3N2 infections in this season and providing important information for developing vaccines that are effective against both genotypes.

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Acknowledgments

We acknowledge the authors and originating and submitting laboratories of the sequences from GISAID’s EpiFlu Database on which this research is based. All submitters of data may be contacted directly via the GISAID website http://www.gisaid.org. This work was supported in part by the BMBF-founded FluResearchNet (Molecular Signatures Determining Pathogenicity and Species Transmission of Influenza A Viruses [01 KI 07136 to S.P.]), a fellowship from the German-Egyptian Research Long-Term Scholarship “GERLS” program co-funded by the Egyptian government and the German Academic Exchange Service (DAAD, to A. M.), and the DFG-funded SFB/TR 84 (Innate Immunity of the Lung: Mechanisms of Pathogen Attack and Host Defence in Pneumonia, TP B2 to S. P.) and SFB 1021 (RNA viruses: RNA metabolism, host response and pathogenesis, TP C1 and TP A1 to S.P. and J.Z.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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    Authors and Affiliations

    1. Institute of Medical Virology, Justus Liebig University Giessen, Schubertstrasse 81, 35392, Giessen, Germany

      Ahmed Mostafa, Heiko Slanina, Irina Kuznetsova, Christian G. Schüttler, John Ziebuhr & Stephan Pleschka

    2. Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Giza, Egypt

      Ahmed Mostafa

    3. Federal Research Institute for Animal Health, Friedrich-Loeffler-Institute, Suedufer 10, 17493, Greifswald, Insel-Riems, Germany

      El-Sayed M. Abdelwhab

    4. Department of Poultry Diseases, National Research Centre (NRC), Dokki, Giza, Egypt

      Mohamed A. Hussein

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    1. Ahmed Mostafa
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    Correspondence to Stephan Pleschka.

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    This article does not contain any studies with human participants or animals performed by any of the authors

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    A. Mostafa and E.-S. M. Abdelwhab equally contributed as first author.

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    Mostafa, A., Abdelwhab, ES.M., Slanina, H. et al. Phylogenetic analysis of human influenza A/H3N2 viruses isolated in 2015 in Germany indicates significant genetic divergence from vaccine strains. Arch Virol 161, 1505–1515 (2016). https://doi.org/10.1007/s00705-016-2815-x

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