Influenza A Virus Infections Sense Host Membrane Tension to Dynamically Tune Assembly

Enveloped viruses often exhibit a pleomorphic morphology, ranging in size from 100nm spheres to tens-of-micron long filaments. For influenza A virus (IAV), spheres enable rapid replication and minimize metabolic cost, while filaments resist effects of antibodies or other cell-entry pressures. The current paradigm is that virion shape changes require genetic adaptation; however, a virus evolved to alter its shape phenotypically would outperform one that relies on genetic selection. Using a novel quantitative flow virometry assay to characterize virion shape dynamics we find that IAV rapidly tunes its shape distribution to favor spheres under optimal, and filaments under attenuating conditions including the presence of antibodies. We identify membrane tension as a key cue sensed by IAV determining shape distributions. This phenotypic shift outpaces genetic change and serves to enable additional life cycles under pressure. Our work expands knowledge of the complex host-virus interplay to include viral responses to the local environment by optimizing its structure to maximize replication and ultimately host-host transmission. ### Competing Interest Statement T.I. is involved on a pending patent related to the flow virometry methodology: PCT/US2022/042125, status pending. The authors declare no other competing interests.