Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
The assembly of Ebola virus nucleocapsid requires virion-associated proteins 35 and 24 and posttranslational modification of nucleoprotein.
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Co-expression of NP, VP35 and VP24 alone is sufficient for spontaneous nucleocapsid assembly in transfected 293T cells, and the three proteins interact specifically.
"Expression of the nucleoprotein (NP) and virion-associated proteins VP35 and VP24 led to spontaneous assembly of nucleocapsids in transfected 293T cells by transmission electron microscopy."
The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3.
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VP35 blocks virus-induced IRF-3 phosphorylation, dimerization and nuclear translocation, and therefore IRF3-dependent host gene induction, but has no effect on the constitutively active IRF-3 5D mutant.
"VP35 blocks virus-induced IRF-3 phosphorylation and subsequent IRF-3 dimerization and nuclear translocation."
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VP35 does not inhibit signalling downstream of the type I interferon receptor, which is the finding that rules out GO:0039502 for this protein.
"Neither the Zaire or Reston VP35 proteins were able to inhibit IFN-β-induced activation of the ISG54 or the ISG56 promoters (Fig. 1C and D)."
Ebola virus VP35 protein binds double-stranded RNA and inhibits alpha/beta interferon production induced by RIG-I signaling.
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VP35 binds duplex RNA specifically and not ssRNA or dsDNA, with R312A and K309A impaired; it blocks RIG-I-induced IRF-3 activation.
"VP35 interacted specifically with poly(rI) · poly(rC), poly(rA) · poly(rU), or in vitro-transcribed dsRNAs derived from EBOV sequences, and not with single-stranded RNAs (ssRNAs) or double-stranded DNA"
Ebola virus protein VP35 impairs the function of interferon regulatory factor-activating kinases IKKepsilon and TBK-1.
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VP35 physically interacts with IKBKE and TBK1, is phosphorylated by them in vitro, displaces IRF-3, IRF-7 and IPS-1 from IKKepsilon, and suppresses the IRF-3-directed kinase activity of IKKepsilon-containing lysates.
"These data suggest that VP35 exerts its IFN-antagonist function, at least in part, by blocking necessary interactions between the kinases IKKepsilon and TBK-1 and their normal interaction partners, including their substrates, IRF-3 and IRF-7."
Ebola Zaire virus blocks type I interferon production by exploiting the host SUMO modification machinery.
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VP35 interacts with IRF7, PIAS1 and Ubc9 and increases PIAS1-mediated SUMOylation of IRF7, repressing interferon transcription; it is not itself a SUMO ligase.
"VP35, while not itself a SUMO ligase, increased PIAS1-mediated SUMOylation of IRF7, and repressed Ifn transcription."
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In Ebola virus it is VP24, not VP35, that blocks the cellular response to secreted interferon.
"VP24 inhibits the cellular response to exogenous IFN by interacting with karyopherin α1, preventing the nuclear accumulation of tyrosine-phosphorylated Stat1 and Stat2"
The VP35 protein of Ebola virus impairs dendritic cell maturation induced by virus and lipopolysaccharide.
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VP35 expressed in mouse dendritic cells prevents virus- and LPS-induced up-regulation of MHC class II, CD40, CD80 and CD86 and of IL-6, IL-12, TNF-alpha and IFN-alpha/beta; the N-terminus is required and the RNA-binding motif is not.
"When expressed in mouse immature DCs, Ebola virus VP35 prevents virus-stimulated expression of CD40, CD80, CD86 and major histocompatibility complex class II."
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VP35-expressing dendritic cells fail to activate allogeneic naive CD4+ T cells, which is the adaptive-immune endpoint of the paper.
"We conclude from these experiments that the VP35 protein attenuates the capacity of DCs to stimulate CD4 + T-cell activation."
Ebolavirus proteins suppress the effects of small interfering RNA by direct interaction with the mammalian RNA interference pathway.
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A screen of all EBOV proteins identified VP35, VP30 and VP40 as suppressors of RNA silencing; VP35 binds the Dicer partners TRBP and PACT independently of siRNA.
"VP35 directly interacts with Dicer partners TRBP and PACT in an siRNA-independent fashion and in the absence of effects on interferon (IFN)."
DRBP76 associates with Ebola virus VP35 and suppresses viral polymerase function.
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DRBP76/ILF3 associates with the VP35 IID and impairs the EBOV transcription/replication complex, acting as an antiviral host factor rather than a VP35 effector.
"These data suggest that DRBP76, via its association with VP35, exerts an anti-EBOV function."
Characterization of the RNA silencing suppression activity of the Ebola virus VP35 protein in plants and mammalian cells.
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Wild-type VP35 blocks establishment of microRNA-directed silencing of a reporter in mammalian cells and has potent silencing-suppressor activity in plants.
"A reporter gene containing specific microRNA target sequences was used to demonstrate that prior expression of wild-type VP35 was able to block establishment of microRNA silencing in mammalian cells."
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Part of the mammalian reporter signal is non-specific translational enhancement rather than silencing suppression, and most of the specific activity is RNA-binding independent.
"The results suggest that enhanced reporter activity in the presence of VP35 is a composite of nonspecific translational enhancement and silencing suppression."
Phosphorylation of Ebola virus VP30 influences the composition of the viral nucleocapsid complex: impact on viral transcription and replication.
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VP35 is one of the four proteins essential for transcription of the EBOV genome and tethers the catalytic polymerase L to the nucleocapsid; VP30 binds the polymerase complex via VP35 in a phosphorylation-dependent way.
"For transcription of the viral genome four viral proteins are essential: the nucleoprotein NP, the polymerase L, the polymerase cofactor VP35, and VP30."
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VP35 is diffusely distributed through the cytoplasm of expressing cells.
"both VP30 and VP35 are diffusely distributed in the cytoplasm preventing colocalization analyses"
Mutual antagonism between the Ebola virus VP35 protein and the RIG-I activator PACT determines infection outcome.
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VP35 disrupts the PACT-RIG-I interaction and inhibits PACT-induced RIG-I ATPase activity; reciprocally, PACT binding costs VP35 its association with the viral polymerase.
"Here, we show that EBOV VP35 inhibits PACT-induced RIG-I ATPase activity in a dose-dependent manner. The interaction of PACT with RIG-I is disrupted by wild-type VP35, but not by VP35 mutants that are unable to bind PACT."
An Intrinsically Disordered Peptide from Ebola Virus VP35 Controls Viral RNA Synthesis by Modulating Nucleoprotein-RNA Interactions.
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VP35 residues 20-48 form an intrinsically disordered NP-binding peptide that binds NP with high affinity, prevents NP oligomerization and releases RNA from NP-RNA complexes, occluding the NP surfaces needed for viral RNA synthesis.
"We identify an intrinsically disordered peptide derived from EBOV VP35 (NPBP, residues 20-48) that binds NP with high affinity and specificity, inhibits NP oligomerization, and releases RNA from NP-RNA complexes in vitro."
The Host E3-Ubiquitin Ligase TRIM6 Ubiquitinates the Ebola Virus VP35 Protein and Promotes Virus Replication.
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VP35 shows a diffuse, slightly granular cytoplasmic localization and is recruited into TRIM6 cytoplasmic bodies on co-expression.
"In contrast, VP35 showed a diffuse, slightly granular cytoplasmic localization, and in some cases it localized in apparent inclusion bodies"
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VP35 is ubiquitinated at K309 by TRIM6, inhibits TRIM6-mediated type I interferon induction, and co-opts TRIM6 to support polymerase activity.
"we also found that TRIM6 enhances EBOV polymerase activity in a minigenome assay and TRIM6 knockout cells have reduced replication of infectious EBOV, suggesting that VP35 hijacks TRIM6 to promote EBOV replication through ubiquitination"