PML mediates the interferon-induced antiviral state against a complex retrovirus via its association with the viral

T Regad1, A Saib, V Lallemand-Breitenbach

  • 1CNRS UPR 9051, Hôpital St Louis, 1 avenue Claude Vellefaux, 75475 Paris Cedex 10, France.

The EMBO Journal
|July 4, 2001
PubMed

Insights

Promyelocytic leukaemia (PML) protein represses human foamy virus (HFV) gene expression by inhibiting viral transcription. Interferon (IFN) treatment inhibits HFV replication in PML-expressing cells, highlighting PML's antiviral role.

Area of Science:

  • Molecular Biology
  • Virology
  • Cell Biology

Background:

  • The promyelocytic leukaemia (PML) protein localizes in the nucleus and forms nuclear bodies (NBs).
  • PML NB formation and intensity increase upon interferon (IFN) stimulation.
  • PML exhibits antiviral activity, though less potent than MxA against certain viruses.

Purpose of the Study:

  • To investigate the role of PML in the gene expression and replication of complex retroviruses, specifically human foamy virus (HFV).
  • To elucidate the mechanism by which PML affects HFV transcription.
  • To determine if PML mediates the antiviral state induced by IFN against HFV.

Main Methods:

  • Overexpression of PML, Mx1, and MxA in cells.
  • Analysis of human foamy virus (HFV) gene expression.
  • Assessment of viral DNA binding by the HFV transactivator, Tas.
  • Experimental use of wild-type and PML-/- cells.
  • Interferon (IFN) treatment of cells.

Main Results:

  • Overexpression of PML, but not Mx1 or MxA, significantly decreased HFV gene expression.
  • PML represses HFV transcription by binding to the HFV transactivator, Tas, preventing its DNA binding.
  • This interaction requires the N-terminal region of Tas and the PML RING finger, independent of PML NB localization.
  • IFN treatment inhibited HFV replication in wild-type cells but not in PML-/- cells.

Conclusions:

  • PML plays a significant role in the transcriptional repression of complex retroviruses like HFV.
  • PML directly interacts with the HFV transactivator, Tas, to inhibit viral transcription.
  • PML is crucial for mediating an IFN-induced antiviral state against HFV, underscoring its importance in innate antiviral immunity.

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