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Article

The HSV-1 Transcription Factor ICP4 Confers Liquid-Like Properties to Viral Replication Compartments

1
Institute of Virology, University of Zurich, CH-8057 Zurich, Switzerland
2
Department of Molecular Life Sciences, University of Zurich, CH-8057 Zurich, Switzerland
3
Institute of Anatomy, University of Zurich, CH-8057 Zurich, Switzerland
4
Molecular, Cellular and Developmental Biology (MCD), Center for Integrative Biology (CBI), University of Toulouse, National Center for Scientific Research (CNRS), 31055 Toulouse, France
*
Author to whom correspondence should be addressed.
Academic Editor: Russell J. Diefenbach
Int. J. Mol. Sci. 2021, 22(9), 4447; https://doi.org/10.3390/ijms22094447
Received: 3 March 2021 / Revised: 18 April 2021 / Accepted: 22 April 2021 / Published: 24 April 2021
(This article belongs to the Special Issue Herpes Simplex Virus: From Reactivation to Assembly)
Herpes Simplex Virus Type-1 (HSV-1) forms progeny in the nucleus within distinct membrane-less inclusions, the viral replication compartments (VRCs), where viral gene expression, DNA replication, and packaging occur. The way in which the VRCs maintain spatial integrity remains unresolved. Here, we demonstrate that the essential viral transcription factor ICP4 is an intrinsically disordered protein (IDP) capable of driving protein condensation and liquid–liquid phase separation (LLPS) in transfected cells. Particularly, ICP4 forms nuclear liquid-like condensates in a dose- and time-dependent manner. Fluorescence recovery after photobleaching (FRAP) assays revealed rapid exchange rates of EYFP-ICP4 between phase-separated condensates and the surroundings, akin to other viral IDPs that drive LLPS. Likewise, HSV-1 VRCs revealed by EYFP-tagged ICP4 retained their liquid-like nature, suggesting that they are phase-separated condensates. Individual VRCs homotypically fused when reaching close proximity and grew over the course of infection. Together, the results of this study demonstrate that the HSV-1 transcription factor ICP4 has characteristics of a viral IDP, forms condensates in the cell nucleus by LLPS, and can be used as a proxy for HSV-1 VRCs with characteristics of liquid–liquid phase-separated condensates. View Full-Text
Keywords: Herpes Simplex Virus Type-1; viral transcription factor; ICP4; intrinsically disordered proteins; liquid–liquid phase separation; viral replication compartments Herpes Simplex Virus Type-1; viral transcription factor; ICP4; intrinsically disordered proteins; liquid–liquid phase separation; viral replication compartments
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MDPI and ACS Style

Seyffert, M.; Georgi, F.; Tobler, K.; Bourqui, L.; Anfossi, M.; Michaelsen, K.; Vogt, B.; Greber, U.F.; Fraefel, C. The HSV-1 Transcription Factor ICP4 Confers Liquid-Like Properties to Viral Replication Compartments. Int. J. Mol. Sci. 2021, 22, 4447. https://doi.org/10.3390/ijms22094447

AMA Style

Seyffert M, Georgi F, Tobler K, Bourqui L, Anfossi M, Michaelsen K, Vogt B, Greber UF, Fraefel C. The HSV-1 Transcription Factor ICP4 Confers Liquid-Like Properties to Viral Replication Compartments. International Journal of Molecular Sciences. 2021; 22(9):4447. https://doi.org/10.3390/ijms22094447

Chicago/Turabian Style

Seyffert, Michael, Fanny Georgi, Kurt Tobler, Laurent Bourqui, Michela Anfossi, Kevin Michaelsen, Bernd Vogt, Urs F. Greber, and Cornel Fraefel. 2021. "The HSV-1 Transcription Factor ICP4 Confers Liquid-Like Properties to Viral Replication Compartments" International Journal of Molecular Sciences 22, no. 9: 4447. https://doi.org/10.3390/ijms22094447

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