Conserved assembly architecture of the essential herpesvirus packaging accessory factor
- 1Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, New Haven, Connecticut, United States of America
- 2Department of Molecular Biology & Biophysics, University of Connecticut School of Medicine, Farmington, Connecticut, United States of America
Abstract
To create a new wave of infectious virions, all herpesviruses require an accessory factor of unknown function to package their viral genomes into nascent capsids. Here, we present cryo-EM structures of the packaging accessory factor from the α-herpesvirus herpes simplex virus type 1 (HSV-1, UL32) and the β-herpesvirus human cytomegalovirus (HCMV, UL52). Unlike homologs from the γ-herpesviruses, neither UL32 nor UL52 form stable homopentameric rings. UL52 forms incomplete pentameric rings lacking one or two protomers. UL32 does not form stable higher-order species, but stabilization through chemical crosslinking revealed a novel quaternary structure where three pentameric rings assemble into a “tripentamer.” Our results reveal that herpesvirus packaging accessory factors adopt distinct oligomeric states but are constrained to pentameric symmetry. Assembly of protomers into a ring creates a positively charged central channel that we show is critical for infectious virus production in HSV-1. Taken together, our study points to a structurally conserved, essential function of packaging accessory factors across the Herpesviridae. Author summary: Herpesviruses are a diverse family of pathogens that drive human disease. At the end of their life cycle, all herpesviruses must actively package their genomes into newly formed capsids. Although some aspects of packaging are conserved with tailed bacteriophages, herpesviruses require an additional packaging accessory factor of unknown function. Here, we present two high-resolution structures of the packaging accessory factor from herpes simplex virus and human cytomegalovirus and identify pentameric symmetry as a unifying structural feature. We propose that the packaging accessory factor oligomerizes to concentrate positively charges in a central channel critical for packaging progression.
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BibTeX
@article{bailey2026conserved,
title = {{Conserved assembly architecture of the essential herpesvirus packaging accessory factor}},
author = {Elizabeth J. Bailey and Swapnil C. Devarkar and Renata Szczepaniak and Laura M. Meißner and Xinyu Chen and Chunxiang Wu and Sandra K. Weller and Yong Xiong and Allison L. Didychuk},
journal = {PLOS Pathogens},
year = {2026},
month = sep,
doi = {10.1371/journal.ppat.1014540},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014540},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Conserved assembly architecture of the essential herpesvirus packaging accessory factor
AU - Elizabeth J. Bailey
AU - Swapnil C. Devarkar
AU - Renata Szczepaniak
AU - Laura M. Meißner
AU - Xinyu Chen
AU - Chunxiang Wu
AU - Sandra K. Weller
AU - Yong Xiong
AU - Allison L. Didychuk
PY - 2026
DA - 2026/09/10
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014540
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014540
AB - To create a new wave of infectious virions, all herpesviruses require an accessory factor of unknown function to package their viral genomes into nascent capsids. Here, we present cryo-EM structures of the packaging accessory factor from the α-herpesvirus herpes simplex virus type 1 (HSV-1, UL32) and the β-herpesvirus human cytomegalovirus (HCMV, UL52). Unlike homologs from the γ-herpesviruses, neither UL32 nor UL52 form stable homopentameric rings. UL52 forms incomplete pentameric rings lacking one or two protomers. UL32 does not form stable higher-order species, but stabilization through chemical crosslinking revealed a novel quaternary structure where three pentameric rings assemble into a “tripentamer.” Our results reveal that herpesvirus packaging accessory factors adopt distinct oligomeric states but are constrained to pentameric symmetry. Assembly of protomers into a ring creates a positively charged central channel that we show is critical for infectious virus production in HSV-1. Taken together, our study points to a structurally conserved, essential function of packaging accessory factors across the Herpesviridae. Author summary: Herpesviruses are a diverse family of pathogens that drive human disease. At the end of their life cycle, all herpesviruses must actively package their genomes into newly formed capsids. Although some aspects of packaging are conserved with tailed bacteriophages, herpesviruses require an additional packaging accessory factor of unknown function. Here, we present two high-resolution structures of the packaging accessory factor from herpes simplex virus and human cytomegalovirus and identify pentameric symmetry as a unifying structural feature. We propose that the packaging accessory factor oligomerizes to concentrate positively charges in a central channel critical for packaging progression.
SN - 1553-7374
ER -