Influenza A virus reassortment in mammals gives rise to genetically distinct within-host subpopulations

• Type of Material: Article
• Authors: Ketaki Ganti, Emory University; Anish Bagga, Emory College of Arts and Sciences; Silvia Carnaccini, University of Georgia; Lucas Ferreri, Emory University; Ginger Geiger, University of Georgia; Joaquin C Joaquin Caceres, University of Georgia; Brittany Seibert, University of Georgia; Yonghai Li, Kansas State University; Liping Wang, University of Missouri; Taeyong Kwon, Kansas State University; Yuhao Li, Kansas State University; Igor Morozov, Kansas State University; Wenjun Ma, University of Missouri; Juergen A Richt, Kansas State University; Daniel R Perez, University of Georgia; Katharina Koelle, Emory University; Anice Lowen, Emory University
• Language: English
• Date: 2022-11-11
• Publisher: NATURE PORTFOLIO
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-022-34611-z
• Title of Journal or Parent Work: NATURE COMMUNICATIONS
• Volume: 13
• Issue: 1
• Start Page: 6846
• End Page: 6846
• Grant/Funding Information: The research was funded by NIH R01 AI127799 (A.C.L.) and the NIH/NIAID Centers of Excellence in Influenza Research and Response (CEIRR), contract numbers 75N93021C00017 (A.C.L., K.K.), 75N93021C00014 (D.R.P.) and 75N93021C00016 (J.A.R., W.M.), and the AMP Core of the Center of Emerging and Zoonotic Infectious Diseases (CEZID) from NIGMS under award number P20GM130448 (J.A.R.).; This project was supported by the Emory University Integrated Cellular Imaging Microscopy Core.
• Keywords: Multidisciplinary Sciences; EVOLUTION; ORIGIN; SEGMENT; SWINE; Science & Technology; TRANSMISSION; DYNAMICS; LOWER RESPIRATORY-TRACT; FERRET; Science & Technology - Other Topics
• Research Categories: Biology, Microbiology; Health Sciences, Immunology

Abstract

Influenza A virus (IAV) genetic exchange through reassortment has the potential to accelerate viral evolution and has played a critical role in the generation of multiple pandemic strains. For reassortment to occur, distinct viruses must co-infect the same cell. The spatio-temporal dynamics of viral dissemination within an infected host therefore define opportunity for reassortment. Here, we used wild type and synonymously barcoded variant viruses of a pandemic H1N1 strain to examine the within-host viral dynamics that govern reassortment in guinea pigs, ferrets and swine. The first two species are well-established models of human influenza, while swine are a natural host and a frequent conduit for cross-species transmission and reassortment. Our results show reassortment to be pervasive in all three hosts but less frequent in swine than in ferrets and guinea pigs. In ferrets, tissue-specific differences in the opportunity for reassortment are also evident, with more reassortants detected in the nasal tract than the lower respiratory tract. While temporal trends in viral diversity are limited, spatial patterns are clear, with heterogeneity in the viral genotypes detected at distinct anatomical sites revealing extensive compartmentalization of reassortment and replication. Our data indicate that the dynamics of viral replication in mammals allow diversification through reassortment but that the spatial compartmentalization of variants likely shapes their evolution and onward transmission.