A SAP30 complex inhibits IFN-beta expression in Rift Valley fever virus infected cells.
| Autor: | Nicolas Le May, Zeyni Mansuroglu, Psylvia Léger, Thibaut Josse, Guillaume Blot, Agnès Billecocq, Ramon Flick, Yves Jacob, Eliette Bonnefoy, Michèle Bouloy |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: | |
| Zdroj: | PLoS Pathogens, Vol 4, Iss 1, p e13 (2008) |
| Druh dokumentu: | article |
| ISSN: | 1553-7366 1553-7374 85870730 |
| DOI: | 10.1371/journal.ppat.0040013 |
| Popis: | Rift Valley fever virus (RVFV) nonstructural protein NSs acts as the major determinant of virulence by antagonizing interferon beta (IFN-beta) gene expression. We demonstrate here that NSs interacts with the host protein SAP30, which belongs to Sin3A/NCoR/HDACs repressor complexes and interacts with the transcription factor YY1 that regulates IFN-beta gene expression. Using confocal microscopy and chromatin immunoprecipitation, we show that SAP30, YY1, and Sin3A-associated corepressor factors strongly colocalize with nuclear NSs filaments and that NSs, SAP30 and Sin3A-associated factors are recruited on the IFN-beta promoter through YY1, inhibiting CBP recruitment, histone acetylation, and transcriptional activation. To ascertain the role of SAP30, we produced, by reverse genetics, a recombinant RVFV in which the interacting domain in NSs was deleted. The virus was unable to inhibit the IFN response and was avirulent for mice. We discuss here the strategy developed by the highly pathogenic RVFV to evade the host antiviral response, affecting nuclear organization and IFN-beta promoter chromatin structure. |
| Databáze: | Directory of Open Access Journals |
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