PML mediates the interferon-induced antiviral state against a complex retrovirus via its association with the viral transactivator.
The promyelocytic leukaemia (PML) protein localizes in the nucleus both in the nucleoplasm and in matrix-associated multiprotein complexes known as nuclear bodies (NBs). The number and the intensity of PML NBs increase in response to interferon (IFN). Overexpression of PML affects the replication of vesicular stomatitis virus and influenza virus. However, PML has a less powerful 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 transactivator, Tas, preventing its direct binding to viral DNA. This physical 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 that IFN treatment inhibits HFV replication in wild-type but not in PML-/- cells. These findings point to a role for PML in transcriptional repression and suggest that PML could play a key role in mediating an IFN-induced antiviral state against a complex retrovirus.
Regad
T
T
CNRS UPR 9051, Hôpital St Louis, 1 avenue Claude Vellefaux, 75475 Paris Cedex 10, France.
Saib
A
A
Lallemand-Breitenbach
V
V
Pandolfi
P P
PP
de Thé
H
H
Chelbi-Alix
M K
MK
D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism*; D001254:Astrocytoma; D016466:CHO Cells; D006224:Cricetinae; D004279:DNA, Viral / Q000235:genetics; D005347:Fibroblasts / Q000502:physiology / Q000821:virology; D019204:GTP-Binding Proteins; D005909:Glioblastoma; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007739:L Cells; D051379:Mice; D018345:Mice, Knockout; D064547:Myxovirus Resistance Proteins; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D016092:Spumavirus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004279:DNA, Viral; D016898:Interferon-alpha; C579071:MX1 protein, human; C579070:Mx1 protein, mouse; D064547:Myxovirus Resistance Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D011506:Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D012194:RNA-Directed DNA Polymerase; D019204:GTP-Binding Proteins