Multiple conformations of trimeric spikes visualized on a non-enveloped virus

Zhang and Cui et al. present in situ cryoEM structures of the trimeric spike of cytoplasmic polyhedrosis virus in both open and close conformations, and demonstrate that spike detachment from the capsid is triggered by the presence of SAM and ATP. Many viruses utilize trimeric spikes to gain entry into host cells. However, without in situ structures of these trimeric spikes, a full understanding of this dynamic and essential process of viral infections is not possible. Here we present four in situ and one isolated cryoEM structures of the trimeric spike of the cytoplasmic polyhedrosis virus, a member of the non-enveloped Reoviridae family and a virus historically used as a model in the discoveries of RNA transcription and capping. These structures adopt two drastically different conformations, closed spike and opened spike, which respectively represent the penetration-inactive and penetration-active states. Each spike monomer has four domains: N-terminal, body, claw, and C-terminal. From closed to opened state, the RGD motif-containing C-terminal domain is freed to bind integrins, and the claw domain rotates to expose and project its membrane insertion loops into the cellular membrane. Comparison between turret vertices before and after detachment of the trimeric spike shows that the trimeric spike anchors its N-terminal domain in the iris of the pentameric RNA-capping turret. Sensing of cytosolic S-adenosylmethionine (SAM) and adenosine triphosphate (ATP) by the turret triggers a cascade of events: opening of the iris, detachment of the spike, and initiation of endogenous transcription.

Automated summary

Zhang and Cui et al. present the in situ cryoEM structures of the trimeric spike of cytoplasmic polyhedrosis virus, revealing its open and close conformations and elucidating the triggering mechanism of spike detachment by SAM and ATP. This study provides important insights into the function of the trimeric spike during viral infections.