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NSs protein of Rift Valley fever virus blocks interferon production by inhibiting host gene transcription

By A. Billecocq, M. Spiegel, P. Vialat, A. Kohl, F. Weber, M. Bouloy and O. Haller


Rift Valley fever virus (RVFV) is an important cause of epizootics and epidemics in Africa and a potential agent of bioterrorism. A better understanding of the factors that govern RVFV virulence and pathogenicity is required, given the urgent need for antiviral therapies and safe vaccines. We have previously shown that RVFV strains with mutations in the NSs gene are excellent inducers of α/β interferon (IFN-α/β) and are highly attenuated in mice. Here, we demonstrate that NSs is sufficient to block IFN-β gene expression at the transcriptional level. In cells transiently expressing NSs, IFN-β transcripts were not inducible by viral infection or by transfection of poly(I:C). NSs with anti-IFN activity accumulated in the nucleus. In contrast, mutant forms of NSs that had lost their IFN-inhibiting activity remained in the cytoplasm, indicating that nuclear localization plays a role. IFN synthesis is regulated by specific transcription factors, including interferon regulatory factor (IRF-3), NF-κB, and AP-1. In the presence of NSs, IRF-3 was still activated and moved to the nucleus. Likewise, NF-κB and AP-1 were activated normally, as shown in electrophoretic mobility shift assays. Moreover, NSs was found to inhibit transcriptional activity of a constitutive promoter, in agreement with recent findings showing that NSs targets the basal cellular transcription factor TFIIH. The present results suggest that NSs, unlike other viral IFN antagonists, does not inhibit IFN-specific transcription factors but blocks IFN gene expression at a subsequent step

Publisher: 'American Society for Microbiology'
Year: 2004
DOI identifier: 10.1128/JVI.78.18.9798-9806.2004
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Provided by: Enlighten
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