Molecular mechanism of M1-mediated influenza A virus assembly

Abstract

Influenza A virus assembly is orchestrated by matrix protein 1 (M1), which engages ribonucleoproteins, mediates glycoprotein incorporation, and scaffolds lipid envelopment, but how these activities are performed and coordinated is unclear. We determined high-resolution structures of M1 within virions, virus-like particles, and in vitro. We found that M1 binds phosphatidylinositol 4,5-bisphosphate at the membrane, oligomerizes through an electrostatic interface, and switches between three alternative conformational states in different regions of the virion. The M1 conformer at the front associates with ribonucleoproteins and initiates budding. In the body of the virion, two conformers alternate to create an extended filament with seam-like discontinuities. Enrichment of the seam-prone conformation at the virion rear induces envelope closure and exposes a binding site for the cytoplasmic tail of neuraminidase (NA) to promote virus release. Conformational switching within a polarized M1 lattice thereby couples organization of the viral components with shaping of the virion architecture.