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

• Published in: Viruses Vol. 11; no. 2; p. 108
• Main Authors: Simon, Bruno, Pichon, Maxime, Valette, Martine, Burfin, Gwendolyne, Richard, Mathilde, Lina, Bruno, Josset, Laurence
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.01.2019; MDPI
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Ambulatory care; Amino Acid Substitution; Amino acids; Bacterial infections; Child; Child, Preschool; Epidemics; Epidemiological Monitoring; epidemiology; Fainting; Female; France - epidemiology; Genetic Variation; Genome, Viral; Genomes; Genomics; High-Throughput Nucleotide Sequencing; Hospitalization; Human health and pathology; Humans; Infant; Infant, Newborn; Infections; Infectious diseases; Influenza; Influenza A Virus, H3N2 Subtype - genetics; Influenza, Human - epidemiology; Influenza, Human - prevention & control; Intensive care; Intensive care units; Life Sciences; Male; Microbiology and Parasitology; Middle Aged; Morbidity; Mortality; Mutation; Next-generation sequencing; NGS; Pathogenesis; Patients; Quantitative Methods; quasispecies; Retrospective Studies; Santé publique et épidémiologie; Seasons; severity; Severity of Illness Index; Surveillance; vaccination; Vaccines; Virology; Virulence; Viruses; Whole Genome Sequencing; Young Adult; France; United States > US; influenza; severity; epidemiology; NGS; quasispecies; vaccination
• DOI: 10.3390/v11020108
• ISSN: 1999-4915

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.