Distinct labeling of host and viral genomes highlights redistribution of nuclear proteins during HSV-1 infection
- 1Duquesne University
Abstract
Herpes simplex virus type 1 (HSV-1) coordinates viral and cellular proteins during infection. While proteins associated with HSV-1 genomes have been identified, changes in proteins associated with the host genome during infection remain poorly understood. We adapted accelerated native isolation of proteins on nascent DNA (aniPOND) to label and purify cellular and viral DNA then identify associated proteins by mass spectrometry. Using this approach, we confirm observations that cellular transcription, DNA replication, and repair proteins are enriched on viral genomes after the onset of viral DNA replication. We assessed how protein interactions with cellular DNA change during infection relative to protein abundance. Targets of the viral E3 ubiquitin ligase, ICP0, are depleted from the nucleus and cellular genome during infection. Transcription regulatory factors, Pol II, and the proteasome are depleted from the host genome, while association with DNA damage response and nuclear pore proteins increases. We also provide evidence for HSV-1 disruption of ribosome biogenesis. Results demonstrate reorganization of the nucleus during infection and validate this technique to identify changes to host genome-associated factors during infection.
Related
- Electrostatic Encoding Enables Simultaneous Dual Labeling of Proteins by a Single Sortase A Enzyme
- Epitope-based labeling for improved live-imaging of endogenous proteins in C. elegans
- Distinct roles of Hsp110 proteins in regulating prion propagation
- Incorporation of genome-bound cellular proteins into HIV-1 particles regulates viral infection
- Persistence of viral full-length genomic RNA and replication-associated RNA transcripts and proteins in sheep tissues following acute Crimean-Congo hemorrhagic fever virus infection
BibTeX
@misc{lloyd2026distinct,
title = {{Distinct labeling of host and viral genomes highlights redistribution of nuclear proteins during HSV-1 infection}},
author = {A. E. Lloyd and J. E. Packard and S. L. Rutan and J. A. Dembowski},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.30.763179},
url = {https://www.biorxiv.org/content/10.64898/2026.10.30.763179v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Distinct labeling of host and viral genomes highlights redistribution of nuclear proteins during HSV-1 infection
AU - A. E. Lloyd
AU - J. E. Packard
AU - S. L. Rutan
AU - J. A. Dembowski
PY - 2026
DA - 2026/10/30
PB - bioRxiv
DO - 10.64898/2026.10.30.763179
UR - https://www.biorxiv.org/content/10.64898/2026.10.30.763179v1
AB - Herpes simplex virus type 1 (HSV-1) coordinates viral and cellular proteins during infection. While proteins associated with HSV-1 genomes have been identified, changes in proteins associated with the host genome during infection remain poorly understood. We adapted accelerated native isolation of proteins on nascent DNA (aniPOND) to label and purify cellular and viral DNA then identify associated proteins by mass spectrometry. Using this approach, we confirm observations that cellular transcription, DNA replication, and repair proteins are enriched on viral genomes after the onset of viral DNA replication. We assessed how protein interactions with cellular DNA change during infection relative to protein abundance. Targets of the viral E3 ubiquitin ligase, ICP0, are depleted from the nucleus and cellular genome during infection. Transcription regulatory factors, Pol II, and the proteasome are depleted from the host genome, while association with DNA damage response and nuclear pore proteins increases. We also provide evidence for HSV-1 disruption of ribosome biogenesis. Results demonstrate reorganization of the nucleus during infection and validate this technique to identify changes to host genome-associated factors during infection.
ER -