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

PLoS Pathog. 2015 Nov 13;11(11):e1005280. doi: 10.1371/journal.ppat.1005280. eCollection 2015 Nov.


PML (Promyelocytic Leukemia protein), also known as TRIM19, belongs to the family of tripartite motif (TRIM) proteins. PML is mainly expressed in the nucleus, where it forms dynamic structures known as PML nuclear bodies that recruit many other proteins, such as Sp100 and Daxx. While the role of PML/TRIM19 in antiviral defense is well documented, its effect on HIV-1 infection remains unclear. Here we show that infection by HIV-1 and other retroviruses triggers the formation of PML cytoplasmic bodies, as early as 30 minutes post-infection. Quantification of the number and size of PML cytoplasmic bodies revealed that they last approximately 8 h, with a peak at 2 h post-infection. PML re-localization is blocked by reverse-transcription inhibitors and is not observed following infection with unrelated viruses, suggesting it is specifically triggered by retroviral reverse-transcription. Furthermore, we show that PML interferes with an early step of retroviral infection since PML knockdown dramatically increases reverse-transcription efficiency. We demonstrate that PML does not inhibit directly retroviral infection but acts through the stabilization of one of its well-characterized partners, Daxx. In the presence of PML, cytoplasmic Daxx is found in the vicinity of incoming HIV-1 capsids and inhibits reverse-transcription. Interestingly, Daxx not only interferes with exogenous retroviral infections but can also inhibit retrotransposition of endogenous retroviruses, thus identifying Daxx as a broad cellular inhibitor of reverse-transcription. Altogether, these findings unravel a novel antiviral function for PML and PML nuclear body-associated protein Daxx.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Nucleus / metabolism
  • HIV-1 / metabolism
  • Humans
  • Nuclear Proteins / metabolism*
  • Promyelocytic Leukemia Protein
  • Protein Binding / physiology
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Tumor Suppressor Proteins / metabolism*


  • Adaptor Proteins, Signal Transducing
  • DAXX protein, human
  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • Transcription Factors
  • Tumor Suppressor Proteins
  • PML protein, human

Grant support

This work was supported by grants from the Agence Nationale de Recherches sur le SIDA et les hépatites virales (ANRS). JD and DMP are funded by ANRS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.