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PML/TRIM19-Dependent Inhibition of Retroviral Reverse-Transcription by Daxx

Jacques Dutrieux1, Ghizlane Maarifi1, Débora M Portilho2

  • 1Paris Descartes University, Paris, France.

Plos Pathogens
|November 14, 2015
PubMed

Insights

Promyelocytic Leukemia protein (PML) forms cytoplasmic bodies during HIV-1 infection, inhibiting viral reverse-transcription through its partner Daxx. This reveals a novel antiviral role for PML and Daxx against retroviruses.

Area of Science:

  • Cell Biology
  • Virology
  • Molecular Biology

Background:

  • Promyelocytic Leukemia protein (PML), also known as TRIM19, is a nuclear protein forming PML nuclear bodies.
  • The antiviral role of PML is known, but its specific impact on HIV-1 infection is unclear.

Purpose of the Study:

  • To investigate the effect of HIV-1 infection on PML localization and function.
  • To elucidate the mechanism by which PML influences retroviral infection.

Main Methods:

  • Monitoring PML localization and PML cytoplasmic body formation post-HIV-1 infection.
  • Using reverse-transcription inhibitors to study PML re-localization triggers.
  • Performing PML knockdown experiments to assess its impact on reverse-transcription efficiency.
  • Investigating the interaction between PML, Daxx, and HIV-1 components.

Main Results:

  • HIV-1 infection triggers the formation of PML cytoplasmic bodies within 30 minutes, peaking at 2 hours and lasting for 8 hours.
  • PML re-localization is specifically dependent on retroviral reverse-transcription.
  • PML knockdown enhances HIV-1 reverse-transcription efficiency, indicating an inhibitory role.
  • PML inhibits retroviral infection by stabilizing cytoplasmic Daxx, which then interferes with reverse-transcription near incoming HIV-1 capsids.
  • Daxx demonstrates broad inhibitory activity against both exogenous and endogenous retroviruses.

Conclusions:

  • PML exhibits a novel antiviral function against HIV-1 by promoting the formation of cytoplasmic bodies.
  • PML-mediated inhibition of retroviral reverse-transcription is dependent on the stabilization of its partner protein, Daxx.
  • Daxx acts as a broad cellular inhibitor of reverse-transcription, impacting both exogenous and endogenous retroviruses.

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