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

Bruno Simon,Bruno Lina,Mathilde Richard,Gwendolyne Burfin,Maxime Pichon,Martine Valette,Laurence Josset

doi:10.3390/v11020108

Abstract

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.

Highlights

Seasonal influenza infections remain a considerable health and socioeconomic challenge, as vaccine uptake and effectiveness are still limited
We describe the genomic characteristics of Influenza A (H3N2) clinical strains recovered via the French national influenza surveillance network or from patients hospitalized in the intensive care units of the University Hospitals of Lyon, France
Samples included in this study were recovered between May 2016 and April 2017 via the French national influenza surveillance network or from patients hospitalized in Lyon University Hospitals

Summary

Introduction

Seasonal influenza infections remain a considerable health and socioeconomic challenge, as vaccine uptake and effectiveness are still limited. 650,000 respiratory deaths worldwide [1] This continuing burden leads to the constant adaptation of public health measures, including vaccination policies which remain the most potentially effective method to limit the impact of influenza [2]. Antivirals that control the infection in some patients at risk of complications are available and usually recommended, yet resistant strains often appear in cases of prolonged treatments. In this context, influenza surveillance is mostly focused on studying antigenic variants to select vaccine strains [5] or resistance mutations to monitor antiviral effectiveness [6,7]

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Conclusion