PMID:15563593

Citation	Andrejeva, J, Childs, KS, Young, DF, Carlos, TS, Stock, N, Goodbourn, S and Randall, RE (2004) The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter. Proc. Natl. Acad. Sci. U.S.A. 101:17264-9
Abstract	Most paramyxoviruses circumvent the IFN response by blocking IFN signaling and limiting the production of IFN by virus-infected cells. Here we report that the highly conserved cysteine-rich C-terminal domain of the V proteins of a wide variety of paramyxoviruses binds melanoma differentiation-associated gene 5 (mda-5) product. mda-5 is an IFN-inducible host cell DExD/H box helicase that contains a caspase recruitment domain at its N terminus. Overexpression of mda-5 stimulated the basal activity of the IFN-beta promoter in reporter gene assays and significantly enhanced the activation of the IFN-beta promoter by intracellular dsRNA. Both these activities were repressed by coexpression of the V proteins of simian virus 5, human parainfluenza virus 2, mumps virus, Sendai virus, and Hendra virus. Similar results to the reporter assays were obtained by measuring IFN production. Inhibition of mda-5 by RNA interference or by dominant interfering forms of mda-5 significantly inhibited the activation of the IFN-beta promoter by dsRNA. It thus appears that mda-5 plays a central role in an intracellular signal transduction pathway that can lead to the activation of the IFN-beta promoter, and that the V proteins of paramyxoviruses interact with mda-5 to block its activity.
Links	PubMed PMC535396 Online version:10.1073/pnas.0407639101
Keywords	Animals; Binding Sites; Cell Line; DEAD-box RNA Helicases; Humans; Interferon-beta/genetics; Paramyxoviridae/chemistry; Promoter Regions, Genetic/drug effects; Protein Binding; RNA Helicases/antagonists & inhibitors; RNA Helicases/genetics; RNA Helicases/metabolism; RNA, Small Interfering/pharmacology; Signal Transduction; Transcriptional Activation/drug effects; Transfection; Viral Proteins/genetics; Viral Proteins/metabolism; Viral Proteins/pharmacology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
9PARA:F8V2V1		GO:0039554: suppression by virus of host MDA-5 activity	ECO:0000314:		P		Fig 5	complete CACAO 6766
9PARA:F8V2V1	involved_in	GO:0039554: suppression by virus of host MDA-5 activity	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:IFIH1		GO:0032897: negative regulation of viral transcription	ECO:0000314:		P		figure 3 electrophoresis inhibiting the promoter for transcription	complete
PIV5:V		GO:0039554: suppression by virus of host MDA-5 activity	ECO:0000314:		P		Fig 3 & 4.	complete CACAO 6765
PIV5:V	involved_in	GO:0039554: suppression by virus of host MDA-5 activity	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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