Near-atomic structures of human astrovirus capsids reveal a subunit-specific maturation mechanism

Authors

Hiraka, K., Burton-Smith, R. N., Song, C., Miyamoto, K., Haga, K., Takai-Todaka, R., Nakanishi, A., Katayama, K., Murata, K.

Abstract

Human astrovirus (HAstV) is a major cause of acute gastroenteritis, yet the structural basis of capsid maturation and infectivity remains poorly understood. Here, we report near-atomic cryo-electron microscopy structures of HAstV serotype 4 in immature and mature states at 1.79 [A] and 1.73 [A] resolution, respectively. These structures reveal a subunit-specific maturation mechanism in which differential protease accessibility drives selective removal of spike (P2) domains. Structural comparisons show that only A-B dimers form a broad cavity beneath the P2 domains that is permissive for trypsin entry, whereas the corresponding region in C-C dimers is sterically restricted. Proteolytic maturation induces pronounced conformational rearrangements, particularly in subunit B, linking capsid geometry to asymmetric protease susceptibility. Despite these changes, the inner capsid architecture and presumptive RNA-associated densities remain conserved, indicating that genome release occurs at a later stage of infection. Together, our findings establish a mechanistic framework in which capsid geometry governs proteolysis-driven activation.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 25 Jun 2026.

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