PMID:16698996

Citation	Reid, SP, Leung, LW, Hartman, AL, Martinez, O, Shaw, ML, Carbonnelle, C, Volchkov, VE, Nichol, ST and Basler, CF (2006) Ebola virus VP24 binds karyopherin alpha1 and blocks STAT1 nuclear accumulation. J. Virol. 80:5156-67
Abstract	Ebola virus (EBOV) infection blocks cellular production of alpha/beta interferon (IFN-alpha/beta) and the ability of cells to respond to IFN-alpha/beta or IFN-gamma. The EBOV VP35 protein has previously been identified as an EBOV-encoded inhibitor of IFN-alpha/beta production. However, the mechanism by which EBOV infection inhibits responses to IFNs has not previously been defined. Here we demonstrate that the EBOV VP24 protein functions as an inhibitor of IFN-alpha/beta and IFN-gamma signaling. Expression of VP24 results in an inhibition of IFN-induced gene expression and an inability of IFNs to induce an antiviral state. The VP24-mediated inhibition of cellular responses to IFNs correlates with the impaired nuclear accumulation of tyrosine-phosphorylated STAT1 (PY-STAT1), a key step in both IFN-alpha/beta and IFN-gamma signaling. Consistent with this proposed function for VP24, infection of cells with EBOV also confers a block to the IFN-induced nuclear accumulation of PY-STAT1. Further, VP24 is found to specifically interact with karyopherin alpha1, the nuclear localization signal receptor for PY-STAT1, but not with karyopherin alpha2, alpha3, or alpha4. Overexpression of VP24 results in a loss of karyopherin alpha1-PY-STAT1 interaction, indicating that the VP24-karyopherin alpha1 interaction contributes to the block to IFN signaling. These data suggest that VP24 is likely to be an important virulence determinant that allows EBOV to evade the antiviral effects of IFNs.
Links	PubMed PMC1472181 Online version:10.1128/JVI.02349-05
Keywords	Animals; Cell Line; Cercopithecus aethiops; Ebolavirus/chemistry; STAT1 Transcription Factor/antagonists & inhibitors; STAT1 Transcription Factor/metabolism; Signal Transduction; Vero Cells; Viral Proteins/pharmacology; alpha Karyopherins/drug effects; alpha Karyopherins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
EBOZM:VP24		GO:0046774: suppression by virus of host intracellular interferon activity	ECO:0000314:		P		Figure 1: ISG54- CAT is a reporter gene that is induced by IFN-β. 1A shows that the expression is inhibited significantly when both VP24 and flagged VP24 are present. STAT1 expression is also induced by IFN-β and is key in the antiviral response. 1B shows a Western blot of STAT1 expression, which is also inhibited by VP24. A Lucerifase reporter was placed under control of a promoter that responds to INF-γ induction and the activity reported in 1C. INF-γ is also inhibited by VP24.	complete CACAO 6388
EBOZM:VP24	involved_in	GO:0046774: suppression by virus of host intracellular interferon activity	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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