Viral expansion after transfer is a primary driver of influenza A virus transmission bottlenecks

• Type of Material: Article
• Authors: Katie E. Holmes, Emory University; David VanInsberghe, Emory University; Lucas Matias Ferreri, Emory University; Baptiste Elie, Université de Montpellier; Ketaki Ganti, Emory University; Chung-Young Lee, Kyungpook National University; Anice Lowen, Emory University
• Language: English
• Date: 2023-12-26
• Publisher: NIH
• Publication Version: Preprint (Prior to Peer Review)
• Copyright Statement: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1101/2023.11.19.567585
• Title of Journal or Parent Work: bioRxiv
• Start Page: 567585
• Grant/Funding Information: This study was supported in part by R01 AI165644 and the National Institute of Allergy and Infectious Diseases (NIAID) Centers of Excellence for Influenza Research and Response (CEIRR) contract no. 75N93021C00017.
• Keywords: narrow bottlenecks; transmission; genetic diversity; influenza
• Research Categories: Biology, Virology

Abstract

For many viruses, narrow bottlenecks acting during transmission sharply reduce genetic diversity in a recipient host relative to the donor. Since genetic diversity represents adaptive potential, such losses of diversity are though to limit the opportunity for viral populations to undergo antigenic change and other adaptive processes. Thus, a detailed picture of evolutionary dynamics during transmission is critical to understanding the forces driving viral evolution at an epidemiologic scale. To advance this understanding, we used a novel barcoded virus library and a guinea pig model of transmission to decipher where in the transmission process diversity is lost for influenza A viruses. In inoculated guinea pigs, we show that a high level of viral genetic diversity is maintained across time. Continuity in the barcodes detected furthermore indicates that stochastic effects are not pronounced within inoculated hosts. Importantly, in both aerosol-exposed and direct contact-exposed animals, we observed many barcodes at the earliest time point(s) positive for infectious virus, indicating robust transfer of diversity through the environment. This high viral diversity is short-lived, however, with a sharp decline seen 1–2 days after initiation of infection. Although major losses of diversity at transmission are well described for influenza A virus, our data indicate that events that occur following viral transfer and during the earliest stages of natural infection have a predominant role in this process. This finding suggests that immune selection may have greater opportunity to operate during influenza A transmission than previously recognized.