A SAP30 Complex Inhibits IFN-β Expression in Rift Valley Fever Virus Infected Cells

PLoS Pathogens

Ramon Flick¹  Eliette Bonnefoy²  Thibaut Josse²  Zeyni Mansuroglu²  Nicolas Le May³  Psylvia Léger³  Michèle Bouloy³  Agnès Billecocq³  Guillaume Blot³  Yves Jacob⁴ 

[1] BioProtection Systems Corporation, Ames, Iowa, United States of America;Régulation de la Transcription et Maladies Génétiques, CNRS UPR2228, UFR Biomédicale, Université Paris Descartes, Paris, France;Unité de Génétique Moléculaire des Bunyavirus, Institut Pasteur, Paris, France;Unité de Génétique, Papillomavirus et Cancer Humain, Institut Pasteur, Paris, France

关键词: Immunoprecipitation;    Rift Valley fever virus;    Transcription factors;    Transcriptional control;    Cell binding;    Confocal microscopy;    Gene expression;    Yeast infections;   

DOI  :  10.1371/journal.ppat.0040013

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Rift Valley fever virus (RVFV) nonstructural protein NSs acts as the major determinant of virulence by antagonizing interferon β (IFN-β) 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-β 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-β 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-β promoter chromatin structure.

【 授权许可】

CC BY