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Open AccessArticle

Whole Genome Sequencing of A(H3N2) Influenza Viruses Reveals Variants Associated with Severity during the 2016–2017 Season

1
Virpath, CIRI, Univ Lyon, Inserm U1111 CNRS UMR5308, ENS, UCBL, Faculté de Médecine Lyon Est, 69372 Lyon, France
2
Laboratoire de Virologie, IAI, CBN, Groupement Hospitalier Nord, Hospices Civils de Lyon, 69317 Lyon, France
3
Centre National des Virus Respiratoires, IAI, CBN, Groupement Hospitalier Nord, Hospices Civils de Lyon, 69317 Lyon, France
4
Department of Viroscience, Erasmus MC, 3000 Rotterdam, The Netherlands
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(2), 108; https://doi.org/10.3390/v11020108
Received: 18 December 2018 / Revised: 21 January 2019 / Accepted: 22 January 2019 / Published: 28 January 2019
(This article belongs to the Section Animal Viruses)
Influenza viruses cause a remarkable disease burden and significant morbidity and mortality worldwide, and these impacts vary between seasons. To understand the mechanisms associated with these differences, a comprehensive approach is needed to characterize the impact of influenza genomic traits on the burden of disease. During 2016–2017, a year with severe A(H3N2), we sequenced 176 A(H3N2) influenza genomes using next generation sequencing (NGS) for routine surveillance of circulating influenza viruses collected via the French national influenza community-based surveillance network or from patients hospitalized in the intensive care units of the University Hospitals of Lyon, France. Taking into account confounding factors, sequencing and clinical data were used to identify genomic variants and quasispecies associated with influenza severity or vaccine failure. Several amino acid substitutions significantly associated with clinical traits were found, including NA V263I and NS1 K196E which were associated with severity and co-occurred only in viruses from the 3c.2a1 clade. Additionally, we observed that intra-host diversity as a whole and on a specific set of gene segments increased with severity. These results support the use of whole genome sequencing as a tool for the identification of genetic traits associated with severe influenza in the context of influenza surveillance. View Full-Text
Keywords: influenza; NGS; severity; vaccination; epidemiology; quasispecies influenza; NGS; severity; vaccination; epidemiology; quasispecies
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Simon, B.; Pichon, M.; Valette, M.; Burfin, G.; Richard, M.; Lina, B.; Josset, L. Whole Genome Sequencing of A(H3N2) Influenza Viruses Reveals Variants Associated with Severity during the 2016–2017 Season. Viruses 2019, 11, 108.

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