PML mediates the interferon-induced antiviral state against a complex retrovirus via its association with the viral transactivator Journal Article
| Authors: | Regad, T.; Saib, A.; Lallemand-Breitenbach, V.; Pandolfi, P. P.; De Thé, H.; Chelbi-Alix, M. K. |
| Article Title: | PML mediates the interferon-induced antiviral state against a complex retrovirus via its association with the viral transactivator |
| 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. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; nonhuman; alpha interferon; proteins; animal cell; mouse; animals; mice; mice, knockout; nuclear protein; embryo; neoplasm proteins; gtp-binding proteins; tumor cells, cultured; transfection; transcription factors; nuclear proteins; transcription regulation; amino terminal sequence; messenger rna; rna, messenger; glioblastoma; transactivator protein; gene repression; tumor suppressor proteins; recombinant proteins; promyelocytic leukemia; transactivation; fibroblasts; virus antigen; dna, viral; trans-activators; virus replication; astrocytoma; knockout mouse; rna, viral; retrovirus; antiviral activity; interferon-alpha; antiviral agents; nbs; cho cell; cho cells; cricetinae; promyelocytic leukemia protein; virus dna; myxovirus resistance protein a; transcriptional repression; cell nucleus inclusion body; humans; human; priority journal; article; virus resistance; protein mx1; spumavirus; spuma virus; hfv; mx; tas; protein tas; l cells (cell line); rna-directed dna polymerase |
| Journal Title: | EMBO Journal |
| Volume: | 20 |
| Issue: | 13 |
| ISSN: | 0261-4189 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2001-07-02 |
| Start Page: | 3495 |
| End Page: | 3505 |
| Language: | English |
| DOI: | 10.1093/emboj/20.13.3495 |
| PUBMED: | 11432836 |
| PROVIDER: | scopus |
| PMCID: | PMC125516 |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work