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Updated: Jun 5, 2026

Temporal Analysis of the Nuclear-to-cytoplasmic Translocation of a Herpes Simplex Virus 1 Protein by Immunofluorescent Confocal Microscopy
06:40

Temporal Analysis of the Nuclear-to-cytoplasmic Translocation of a Herpes Simplex Virus 1 Protein by Immunofluorescent Confocal Microscopy

Published on: November 4, 2018

PML isoforms I and II participate in PML-dependent restriction of HSV-1 replication

Delphine Cuchet1, Amanda Sykes, Armel Nicolas

  • 1MRC-University of Glasgow Centre for Virus Research, Church Street, Glasgow G11 5JR, Scotland, UK.

Journal of Cell Science
|December 22, 2010
PubMed

Insights

Promyelocytic leukaemia (PML) nuclear bodies restrict herpes simplex virus type 1 (HSV-1) replication. Specific PML isoforms, particularly isoform I, can restore antiviral resistance by interacting with viral proteins.

Area of Science:

  • Cellular biology
  • Virology
  • Molecular biology

Background:

  • Intrinsic antiviral resistance is crucial for host defense against viral infections.
  • Promyelocytic leukaemia nuclear bodies (PML-NBs), also known as ND10, are key cellular structures involved in restricting herpes simplex virus type 1 (HSV-1) replication.
  • The viral protein ICP0 counteracts the antiviral mechanisms mediated by PML-NBs.

Purpose of the Study:

  • To investigate the role of individual promyelocytic leukaemia (PML) isoforms in antiviral defense against HSV-1.
  • To elucidate the molecular mechanisms by which PML isoforms exert their antiviral activity, focusing on PML isoform I.
  • To understand how PML-NB composition and modification are affected by individual PML isoforms.

Main Methods:

  • PML depletion and re-expression of individual PML isoforms in cellular models.
  • Analysis of HSV-1 plaque formation in PML-depleted cells.
  • Immunofluorescence microscopy to assess PML-NB formation, composition, and colocalization with other ND10 components.
  • Investigation of the role of SUMO modification and the SUMO-interaction motif (SIM) in PML isoform I activity.

Main Results:

  • Depletion of all PML isoforms reduces cellular resistance to ICP0-null mutant HSV-1.
  • Individual expression of PML isoforms I and II partially restores resistance to ICP0-null mutant HSV-1 in PML-depleted cells.
  • The antiviral activity of PML isoform I depends on SUMO modification, its SIM, and its TRIM domain.
  • Individual PML isoforms form distinct foci with subtle differences in composition and Sp100 modification compared to normal ND10.
  • Deletion of the SIM motif from PML isoform I enhances its colocalization with other ND10 components in PML-deficient cells.

Conclusions:

  • Complete PML functionality in antiviral defense relies on isoform-specific C-terminal sequences acting in concert.
  • PML isoforms exhibit distinct properties in ND10 formation and antiviral activity.
  • SUMOylation and the SIM motif are critical for the antiviral function of PML isoform I.

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