Molecular architecture of Influenza A virions

Influenza A viruses (IAV) are clinically important pathogens that cause seasonal epidemics and pandemics in humans. IAV produce pleomorphic, enveloped virions, which can range from a spherical or bacilliform morphology, the predominant form in the most commonly studied laboratory strains, to long filamentous virions which are characteristic of clinical and veterinary isolates. Understanding the structure and function of filamentous virions is crucial for clarifying their role in viral persistence and immune evasion, and for informing the development of therapeutics that target their entry and/or egress pathways. Structural characterisation of influenza virions is challenging however owing to their fragility, heterogeneity and compared to most virus particles, unusually large size. Here, we combined structural and compositional approaches with integrative modelling to define the complete molecular architecture of influenza virions. In doing so we provide the first description of distinctive structural features of IAV filaments, including the selective incorporation of lipids, specific enrichment of viral and host proteins, and a viral cytoskeleton including a secondary helical layer within the viral capsid and extended fibrils of cofilactin. Collectively our findings suggest an important regulatory role for cofilactin in driving filament morphogenesis and provide important insights into the organisation and composition of IAV filamentous virions.