Partlow Edward A, Jaeggi-Wong Anna, Planitzer Steven D, Berg Nick, Li Zhenyu, Ivanovic Tijana
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Martin A. Fisher School of Physics, Brandeis University, Waltham, MA, USA.
Nat Microbiol. 2025 Mar;10(3):784-794. doi: 10.1038/s41564-025-01925-9. Epub 2025 Feb 10.
Enveloped viruses such as influenza A virus (IAV) often produce a mixture of virion shapes, ranging from 100 nm spheres to micron-long filaments. Spherical virions use fewer resources, while filamentous virions resist cell-entry pressures such as antibodies. While shape changes are believed to require genetic adaptation, the mechanisms of how viral mutations alter shape remain unclear. Here we find that IAV dynamically adjusts its shape distribution in response to environmental pressures. We developed a quantitative flow virometry assay to measure the shape of viral particles under various infection conditions (such as multiplicity, replication inhibition and antibody treatment) while using different combinations of IAV strains and cell lines. We show that IAV rapidly tunes its shape distribution towards spheres under optimal conditions but favours filaments under attenuation. Our work demonstrates that this phenotypic flexibility allows IAV to rapidly respond to environmental pressures in a way that provides dynamic adaptation potential in changing surroundings.
诸如甲型流感病毒(IAV)之类的包膜病毒通常会产生多种病毒粒子形状的混合物,范围从100纳米的球体到微米长的丝状。球形病毒粒子消耗的资源较少,而丝状病毒粒子则能抵抗诸如抗体等细胞进入压力。虽然形状变化被认为需要基因适应,但病毒突变如何改变形状的机制仍不清楚。在这里,我们发现IAV会根据环境压力动态调整其形状分布。我们开发了一种定量流动病毒形态测定法,以测量在各种感染条件下(如感染复数、复制抑制和抗体处理)病毒粒子的形状,同时使用不同组合的IAV毒株和细胞系。我们表明,IAV在最佳条件下会迅速将其形状分布调整为球体,但在减毒情况下则倾向于丝状。我们的工作表明,这种表型灵活性使IAV能够以一种在不断变化的环境中提供动态适应潜力的方式快速响应环境压力。