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

Area of Science:

• Structural biology
• Virology
• Molecular mechanisms of viral entry

Background:

• Viruses use trimeric spikes for host cell entry, a process poorly understood without in situ structural data.
• Cytoplasmic polyhedrosis virus (CPV), a non-enveloped Reoviridae family member, is a model for RNA transcription and capping discoveries.

Purpose of the Study:

• To determine the in situ structures of CPV trimeric spikes.
• To elucidate the conformational changes and molecular mechanisms underlying viral entry and transcription initiation.

Main Methods:

• Four in situ and one isolated cryo-electron microscopy (cryoEM) structures of CPV trimeric spikes.
• Comparative structural analysis of closed and opened spike conformations.

Main Results:

• CPV trimeric spikes exist in two distinct conformations: closed (inactive) and opened (active).
• The opened conformation facilitates RGD motif binding to integrins and membrane insertion via claw domain rotation.
• Spike detachment from the RNA-capping turret is triggered by S-adenosylmethionine (SAM) and adenosine triphosphate (ATP) binding, initiating transcription.

Conclusions:

• The study provides high-resolution structures of CPV spikes in distinct functional states.
• These structures reveal the dynamic process of viral entry and the linkage between spike detachment and transcription initiation.