2. Academic Validation
  3. Herpes simplex virus-1 fluidizes the nucleus enabling condensate formation

Herpes simplex virus-1 fluidizes the nucleus enabling condensate formation

  • bioRxiv. 2025 Jun 21:2025.06.20.660750. doi: 10.1101/2025.06.20.660750.
Nora L Herzog 1 2,  Gururaj R Kidiyoor 1,  Sarah Keegan 1,  Farah Korchi 3,  David M Chenoweth 4,  Huaiying Zhang 5,  Ian Mohr 2,  Angus Wilson 2,  Liam J Holt 1 6
Affiliations

Affiliations

  • 1 Institute for Systems Genetics, New York University Langone Health, 435 E 30th Street, New York NY 10016, USA.
  • 2 Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
  • 3 Université Paris Cité, Magistère Européen de Génétique, 85 Boulevard Saint-Germain 75006 Paris, France.
  • 4 University of Pennsylvania, Department of Chemistry 231 S. 34 Street Philadelphia, PA 19104-6323, USA.
  • 5 Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213-2617, USA.
  • 6 Department of Biochemistry and Molecular Pharmacology, New York University Langone Health, 435 E 30th Street, New York NY 10016, USA.
PMID: 40667204 DOI: 10.1101/2025.06.20.660750
Abstract

Molecular processes are profoundly influenced by the biophysical properties of the cell interior. However, the mechanisms that control these physical properties, and the processes they impact remain poorly understood, especially in the nucleus. We hypothesized that some viruses might change the biophysical properties of the nucleus to favor virus survival and replication and found that herpes simplex virus 1 (HSV-1) increases the mesoscale fluidity of the nucleus. The HSV-1 protein ICP4 caused fluidization and enabled growth of synthetic nuclear condensates. Conversely, conditions that decreased nuclear fluidity inhibited the formation of viral replication compartment condensates and reduced infectious virus production. Together, our data suggest that ICP4 increases nuclear fluidity to promote the formation of condensates that drive the progression of the HSV-1 life cycle. We speculate that a key function of ICP4 is to overcome the crowding and elastic confinement within cell nuclei that are a fundamental barrier to virus replication.

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