T. Regad et al., PML mediates the interferon-induced antiviral state against a complex retrovirus via its association with the viral transactivator, EMBO J, 20(13), 2001, pp. 3495-3505
The promyelocytic leukaemia (PML) protein localizes in the nucleus both in
the nucleoplasm and in matrix-associated multiprotein complexes known as nu
clear bodies (NBs), The number and the intensity of PML NBs increase in res
ponse to interferon (IFN), Overexpression of PML affects the replication of
vesicular stomatitis virus and influenza virus. However, PML has a less po
werful antiviral activity against these viruses than the IFN mediator MxA,
Here, we show that overexpression of PML, but not that of Mx1 or MxA, leads
to a drastic decrease of a complex retrovirus, the human foamy virus (HFV)
, gene expression. PML represses HFV transcription by complexing the HFV tr
ansactivator, Tas, preventing its direct binding to viral DNA. This physica
l interaction requires the N-terminal region of Tas and the RING finger of
PML, but does not necessitate PML localization in NBs, Finally, we show tha
t IFN treatment inhibits HFV replication in wild-type but not in PML-/- cel
ls. These findings point to a role for PML in transcriptional repression an
d suggest that PML could play a key role in mediating an IFN-induced antivi
ral state against a complex retrovirus.