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

Animals Cell Nucleus / metabolism Chlorocebus aethiops Gene Expression Regulation, Viral Herpes Simplex / genetics Herpesvirus 1, Human / physiology Immediate-Early Proteins / genetics Intrinsically Disordered Proteins / genetics Liquid-Liquid Extraction Phase Transition Vero Cells Viral Replication Compartments
Herpes Simplex Virus Type-1 ICP4 intrinsically disordered proteins liquid–liquid phase separation viral replication compartments viral transcription factor

Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
24 Apr 2021
Historique:
received: 03 03 2021
revised: 18 04 2021
accepted: 22 04 2021
entrez: 30 4 2021
pubmed: 1 5 2021
medline: 15 5 2021
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.3390/ijms22094447 PMID: 33923223 PMC: PMC8123221
pubmed: 33923223
pii: ijms22094447
doi: 10.3390/ijms22094447
pmc: PMC8123221
pii:
doi:

Substances chimiques

Immediate-Early Proteins 0
Intrinsically Disordered Proteins 0
herpes simplex virus, type 1 protein ICP4 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Universität Zürich
ID : FK-18-062

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Auteurs

Michael Seyffert (M)

Institute of Virology, University of Zurich, CH-8057 Zurich, Switzerland.
ORCID: 0000-0001-7483-2430

Fanny Georgi (F)

Department of Molecular Life Sciences, University of Zurich, CH-8057 Zurich, Switzerland.
ORCID: 0000-0002-4803-5099

Kurt Tobler (K)

Institute of Virology, University of Zurich, CH-8057 Zurich, Switzerland.
ORCID: 0000-0002-0013-7993

Laurent Bourqui (L)

Institute of Anatomy, University of Zurich, CH-8057 Zurich, Switzerland.

Michela Anfossi (M)

Institute of Virology, University of Zurich, CH-8057 Zurich, Switzerland.
Molecular, Cellular and Developmental Biology (MCD), Center for Integrative Biology (CBI), University of Toulouse, National Center for Scientific Research (CNRS), 31055 Toulouse, France.

Kevin Michaelsen (K)

Institute of Virology, University of Zurich, CH-8057 Zurich, Switzerland.

Bernd Vogt (B)

Institute of Virology, University of Zurich, CH-8057 Zurich, Switzerland.

Urs F Greber (UF)

Department of Molecular Life Sciences, University of Zurich, CH-8057 Zurich, Switzerland.
ORCID: 0000-0003-2278-120X

Cornel Fraefel (C)

Institute of Virology, University of Zurich, CH-8057 Zurich, Switzerland.
ORCID: 0000-0001-7221-6706

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › The HSV-1 Transcription Factor ICP4 Confers...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Noyau de la cellule › The HSV-1 Transcription Factor ICP4 Confers...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Cercopithecidae › Cercopithecinae › Cercopithecus › Cercopithecus aethiops › The HSV-1 Transcription Factor ICP4 Confers...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes viraux › The HSV-1 Transcription Factor ICP4 Confers...
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Infections de la peau › Dermatoses virales › Herpès › The HSV-1 Transcription Factor ICP4 Confers...
questionsmedicales.fr › Virus › Virus à ADN › Herpesviridae › Alphaherpesvirinae › Simplexvirus › Herpèsvirus humain de type 1 › The HSV-1 Transcription Factor ICP4 Confers...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines virales › Protéines virales régulatrices ou accessoires › Protéines précoces immédiates › The HSV-1 Transcription Factor ICP4 Confers...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines intrinsèquement désordonnées › The HSV-1 Transcription Factor ICP4 Confers...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Fractionnement chimique › Extraction liquide-liquide › The HSV-1 Transcription Factor ICP4 Confers...
questionsmedicales.fr › Phénomènes chimiques › Transition de phase › The HSV-1 Transcription Factor ICP4 Confers...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules Vero › The HSV-1 Transcription Factor ICP4 Confers...
questionsmedicales.fr › Phénomènes microbiologiques › Phénomènes physiologiques viraux › Corps d'inclusion viraux › Compartiments de réplication virale › The HSV-1 Transcription Factor ICP4 Confers...