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PMID: 11432836 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 20 ·No. 13 ·2001-07-02 ·Pages 3495-505

Regad T, Saib A, Lallemand-Breitenbach V, Pandolfi PP, de Thé H, Chelbi-Alix MK

Abstract

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.

MeSH Terms
Animals Antiviral Agents/metabolism Astrocytoma CHO Cells Cricetinae DNA, Viral/genetics Fibroblasts/physiology,virology GTP-Binding Proteins Glioblastoma Humans Interferon-alpha/pharmacology L Cells Mice Mice, Knockout Myxovirus Resistance Proteins Neoplasm Proteins/genetics,metabolism Nuclear Proteins/metabolism Promyelocytic Leukemia Protein Proteins/metabolism RNA, Messenger/genetics RNA, Viral/genetics RNA-Directed DNA Polymerase/metabolism Recombinant Proteins/metabolism Spumavirus/drug effects,genetics,physiology Trans-Activators/metabolism Transcription Factors/genetics,metabolism Transfection Tumor Cells, Cultured Tumor Suppressor Proteins Virus Replication/drug effects
Chemicals
Antiviral Agents DNA, Viral Interferon-alpha MX1 protein, human Mx1 protein, mouse Myxovirus Resistance Proteins Neoplasm Proteins Nuclear Proteins Pml protein, mouse Promyelocytic Leukemia Protein Proteins RNA, Messenger RNA, Viral Recombinant Proteins Trans-Activators Transcription Factors Tumor Suppressor Proteins PML protein, human RNA-Directed DNA Polymerase GTP-Binding Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Regad T
CNRS UPR 9051, Hôpital St Louis, 1 avenue Claude Vellefaux, 75475 Paris Cedex 10, France.
Saib A
Lallemand-Breitenbach V
Pandolfi P P
de Thé H
Chelbi-Alix M K
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/20.13.3495
Published
2001-07-02
Pages
3495-505
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125516
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/20.13.3495 PMC Full Text View journal details
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