Influenza A virus within-host evolution and positive selection in a densely sampled household cohort over three seasons

• Published in: Virus evolution 2024-10, Vol.10 (1), p.veae084
• Main Authors: Bendall, Emily E, Zhu, Yuwei, Fitzsimmons, William J, Rolfes, Melissa, Mellis, Alexandra, Halasa, Natasha, Martin, Emily T, Grijalva, Carlos G, Talbot, H Keipp, Lauring, Adam S
• Format: Article
• Language: English
• ISSN: 2057-1577; 2057-1577
• DOI: 10.1093/ve/veae084

Abstract While influenza A virus (IAV) antigenic drift has been documented globally, in experimental animal infections, and in immunocompromised hosts, positive selection has generally not been detected in acute infections. This is likely due to challenges in distinguishing selected rare mutations from sequencing error, a reliance on cross-sectional sampling, and/or the lack of formal tests of selection for individual sites. Here, we sequenced IAV populations from 346 serial, daily nasal swabs from 143 individuals collected over three influenza seasons in a household cohort. Viruses were sequenced in duplicate, and intrahost single nucleotide variants (iSNVs) were identified at a 0.5% frequency threshold. Within-host populations exhibited low diversity, with >75% mutations present at 18 years, 4.4 × 10−6 vs. 9.42 × 10−7 and 3.45 × 10−6, P