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Conserved assembly architecture of the essential herpesvirus packaging accessory factor
Elizabeth J Bailey1, Swapnil C Devarkar1, Renata Szczepaniak2
1Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, New Haven, CT 06511, USA.
Biorxiv : the Preprint Server for Biology
|February 6, 2026
Summary
Herpesviruses need accessory factors to package genomes. Cryo-EM structures reveal these factors form distinct ring structures critical for infectious virus production across the Herpesviridae family.
Area of Science:
- Structural biology
- Virology
- Molecular biology
Background:
- Herpesviruses require accessory factors for genome packaging into capsids.
- The function of these packaging accessory factors remains largely unknown.
- These factors are essential for the production of infectious virions.
Purpose of the Study:
- To determine the structures of packaging accessory factors from herpes simplex virus type 1 (HSV-1, UL32) and human cytomegalovirus (HCMV, UL52).
- To elucidate the oligomeric states and quaternary structures of these essential viral proteins.
- To understand the conserved function of these factors across the Herpesviridae family.
Main Methods:
- Cryo-electron microscopy (cryo-EM) to determine high-resolution structures.
- Chemical crosslinking to stabilize and analyze protein quaternary structures.
- Functional assays in HSV-1 to assess the importance of the central channel.
Main Results:
- Cryo-EM structures of HSV-1 UL32 and HCMV UL52 packaging accessory factors were determined.
- Neither UL32 nor UL52 form stable homopentameric rings, unlike γ-herpesvirus homologs.
- UL52 forms incomplete pentameric rings, while UL32 forms a novel "tripentamer" structure.
- A positively charged central channel formed by ring assembly is essential for HSV-1 infectious virus production.
Conclusions:
- Herpesvirus packaging accessory factors exhibit distinct oligomeric states but share pentameric symmetry constraints.
- The formation of a charged central channel is a conserved mechanism critical for infectious virus production.
- This study reveals a structurally conserved and essential function of packaging accessory factors across the Herpesviridae family.
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