HSV-1 ICP0 expression induces formation of nuclear TDP-43 assemblies
- 1Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
- 2Department of Microbiology, New York University School of Medicine, New York, NY USA
- 3Institute for Systems Genetics, New York University Langone Health, New York, NY USA
Abstract
Toxic cytoplasmic aggregates containing the nuclear RNA-binding protein TDP-43 form in several neurodegenerative diseases; however, the molecular triggers driving aggregation remain unclear. Epidemiological evidence has linked latent and reactivating herpes simplex virus type-1 (HSV-1) infections to neurodegenerative disease onset, but it is unknown if HSV-1 infection impacts TDP-43 subcellular distribution. Here, we demonstrate that HSV-1 infection of epithelial cells and DRG-derived neurons results in nuclear TDP-43 redistribution and TDP-43 accumulation within distinct nuclear assemblies. Cytoplasmic TDP-43 was not detected under these conditions. Nuclear TDP-43 assembly occurred early in infection and was dependent upon expression of the critical ICP0 regulatory gene. Remarkably, ectopic ICP0 expression in uninfected cells was sufficient for nuclear TDP-43 assembly. Thus, expression of a single viral gene product encoded by a near ubiquitous human herpesvirus can alter TDP-43 nuclear localization. Moreover, our work identifies a potential mechanistic link between herpesvirus infection and neuronal disease factor mislocalization.
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BibTeX
@article{braspenning2026hsv1,
title = {{HSV-1 ICP0 expression induces formation of nuclear TDP-43 assemblies}},
author = {Shirley E. Braspenning and Adam T. Silhavy and Nora L. Herzog and Phoebe A. Chen and Angus C. Wilson and Ian J. Mohr},
journal = {Journal of Neurovirology},
year = {2026},
month = oct,
doi = {10.1007/s13365-026-01349-z},
url = {https://doi.org/10.1007/s13365-026-01349-z},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - HSV-1 ICP0 expression induces formation of nuclear TDP-43 assemblies
AU - Shirley E. Braspenning
AU - Adam T. Silhavy
AU - Nora L. Herzog
AU - Phoebe A. Chen
AU - Angus C. Wilson
AU - Ian J. Mohr
PY - 2026
DA - 2026/10/26
JO - Journal of Neurovirology
DO - 10.1007/s13365-026-01349-z
UR - https://doi.org/10.1007/s13365-026-01349-z
AB - Toxic cytoplasmic aggregates containing the nuclear RNA-binding protein TDP-43 form in several neurodegenerative diseases; however, the molecular triggers driving aggregation remain unclear. Epidemiological evidence has linked latent and reactivating herpes simplex virus type-1 (HSV-1) infections to neurodegenerative disease onset, but it is unknown if HSV-1 infection impacts TDP-43 subcellular distribution. Here, we demonstrate that HSV-1 infection of epithelial cells and DRG-derived neurons results in nuclear TDP-43 redistribution and TDP-43 accumulation within distinct nuclear assemblies. Cytoplasmic TDP-43 was not detected under these conditions. Nuclear TDP-43 assembly occurred early in infection and was dependent upon expression of the critical ICP0 regulatory gene. Remarkably, ectopic ICP0 expression in uninfected cells was sufficient for nuclear TDP-43 assembly. Thus, expression of a single viral gene product encoded by a near ubiquitous human herpesvirus can alter TDP-43 nuclear localization. Moreover, our work identifies a potential mechanistic link between herpesvirus infection and neuronal disease factor mislocalization.
SN - 1355-0284
SN - 1538-2443
ER -