PMID:15331713

Citation	Billecocq, A, Spiegel, M, Vialat, P, Kohl, A, Weber, F, Bouloy, M and Haller, O (2004) NSs protein of Rift Valley fever virus blocks interferon production by inhibiting host gene transcription. J. Virol. 78:9798-806
Abstract	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 alpha/beta interferon (IFN-alpha/beta) and are highly attenuated in mice. Here, we demonstrate that NSs is sufficient to block IFN-beta gene expression at the transcriptional level. In cells transiently expressing NSs, IFN-beta 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-kappaB, and AP-1. In the presence of NSs, IRF-3 was still activated and moved to the nucleus. Likewise, NF-kappaB 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.
Links	PubMed PMC514997 Online version:10.1128/JVI.78.18.9798-9806.2004
Keywords	Amino Acid Sequence; Animals; Cell Line; Cercopithecus aethiops; Gene Expression; Humans; Interferon Type I/biosynthesis; Interferon Type I/genetics; Mice; Molecular Sequence Data; Mutation; Promoter Regions, Genetic; Rift Valley fever virus/genetics; Rift Valley fever virus/pathogenicity; Rift Valley fever virus/physiology; Transcriptional Activation; Vero Cells; Viral Nonstructural Proteins/genetics; Viral Nonstructural Proteins/physiology
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RVFVZ:NSS	involved_in	GO:0039653: suppression by virus of host transcription	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
RVFVZ:NSS		GO:0039653: suppression by virus of host transcription	ECO:0000315:		P		Fig. 3A: cells were transfected with various NSs plasmids and luciferase reporter genes under the control of interferon promoters before being stimulated, cells expressing wildtype NSs had little luciferase activity while cells expressing mutant NSs had luciferase activity similar to that of control Fig. 3B: cells were transfected with various NSs plasmids and a pβGal plasmid, cells expressing wildtype NSs had little β-gal activity while cells expressing mutant NSs had β-gal activity similar to that of control	complete CACAO 9743
RVFVZ:NSS		GO:0039501: suppression by virus of host type I interferon production	ECO:0000315:		P		Fig. 1A and 1B: IFN-beta mRNA was produced by cells infected with mutant, wasn't produced by cells infected with wildtype Fig. 1D: cells were transfected with IFN-beta promoter-luciferase plasmids and infected with RVFV strains, luciferase activity in wildtype was 1/5 that of mutant	complete CACAO 9895
RVFVZ:NSS	involved_in	GO:0039501: suppression by virus of host type I interferon production	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

See Help:References for how to manage references in GONUTS.