ライフサイエンスコーパス: IRF-3

1 presence of interferon regulatory factor 3 (IRF-3).

2 gradation of interferon regulatory factor 3 (IRF-3).

3 y inhibiting interferon regulatory factor 3 (IRF-3).

4 of STAT-1 or interferon regulatory factor 3 (IRF-3).

5 s the direct action of caspase-8 cleavage on IRF-3.

6 ation and proteasome-mediated degradation of IRF-3.

7 onents required for the apoptotic pathway of IRF-3.

8 own pathway of transcriptional activation of IRF-3.

9 PKR kinase and interferon regulatory factor IRF-3.

10 endent activities, as exemplified by PKR and IRF-3.

11 s a coinfection model through suppression of IRF-3.

12 n of the transcription factors NF-kappaB and IRF-3.

13 to impair phosphorylation and activation of IRF-3.

14 oth of which activate ISG expression through IRF-3.

15 PRDI site is similar to that of inactivated IRF-3.

16 hich enabled us to express various levels of IRF-3.

17 TING and mediates the activation of TBK1 and IRF-3.

18 uption of the activation and localization of IRF-3.

19 residues 2067-2112) interacts directly with IRF-3 (173-427) and six of its single-site mutants to fo

20 -8, IL-12 p70, and TNF were also observed in Irf-3(-/-)7(-/-) mice 24 hpi, at which time point viral

21 Double-deficient Irf-3(-/-)7(-/-) mice infected with the DENV2 strain S22

22 timulated gene induction was also delayed in Irf-3(-/-)7(-/-) mice relative to wild-type and single-d

23 independently of both IRF-3 and IRF-7 in the Irf-3(-/-)7(-/-) mice with DENV infection.

24 ENV infection, whereas in the Irf-7(-/-) and Irf-3(-/-)7(-/-) mice, significantly low levels of IFN-a

25 CR3 function to restrict DENV replication in Irf-3(-/-)7(-/-) mice.

26 IRF-3(-/-) and select IRF-3/7(-/-) mice were resistant to LP-BM5-induced patho

27 nduced assembly of the transcription factors IRF-3/7, ATF-2/c-Jun, and NF-kappaB on the ifnbeta promo

28 cal MAVS effectors TNFR-associated factor-2, IRF-3/7, or IFN-beta but the physical interaction of MAV

29 phosphorylation of IFN-regulatory factor 3 (IRF-3), a transcription factor that is crucial for the i

30 irus VP35 protein inhibits the activation of IRF-3, a critical transcription factor for the induction

31 IRF-3, a member of the interferon regulatory factor (IRF

32 cells indicated that the amount of residual IRF-3 activated by endogenous SeV was high enough to dri

33 primary mouse macrophages resulted in robust IRF-3 activation and approximately 750-fold increase in

34 ugh cytoplasmic STING, which is required for IRF-3 activation and signaling.

35 retinoic acid-inducible gene I and inducing IRF-3 activation and the synthesis of ISGs that restrict

36 in response to TLR4 ligands HMGB1 and LPS, p-IRF-3 activation and transcription of its target genes a

37 disrupted signal transduction downstream of IRF-3 activation and was independent of capsid-mediated

38 ence in the initial interferon induction via IRF-3 activation between ANDV and PHV in infected primar

39 IRF-3 activation did not correlate with reductions in NS

40 ts indicate that HCV can transiently trigger IRF-3 activation during virus spread and that in chronic

41 Here, we have reported that the pathway of IRF-3 activation in RIPA was independent of and distinct

42 The capacity to rescue IRF-3 activation in these cells was assessed by monitori

43 ent of IRF-3's transcriptional role, a novel IRF-3 activation pathway causes its interaction with the

44 By contrast, the full IRF-3 activation response was largely abolished in PKR-d

45 The DeltaE3L virus-induced IRF-3 activation seen in PKR-sufficient cells was dimini

46 optosis in virus-infected cells by mediating IRF-3 activation through the mitochondrial IPS-1 signal

47 In contrast, IRF-3 activation was essential, although induction of th

48 during virus spread and that in chronic HCV, IRF-3 activation within infected hepatocytes occurs but

49 HCV stimulated a low-frequency and transient IRF-3 activation within responsive cells in vitro that w

50 (HCV) nonstructural 3 protein, the status of IRF-3 activation, and expression of IRF-3 target genes a

51 cate that Ser386 and Ser396 are critical for IRF-3 activation, and support a phosphorylation-oligomer

52 the protein kinase regulated by RNA (PKR) in IRF-3 activation, HeLa cells made stably deficient in PK

53 ral signaling protein (MAVS) but upstream of IRF-3 activation, while GDVII L acts downstream of IRF-3

54 activation, while GDVII L acts downstream of IRF-3 activation.

55 nhancer of activated B cells (NF-kappaB) and IRF-3 activation.

56 s blockage did not inhibit JNK activation or IRF-3 activation.

57 n VP35 renders the protein unable to inhibit IRF-3 activation.

58 a phosphorylation-oligomerization model for IRF-3 activation.

59 Interferon regulatory factor-3 (IRF-3) activation directs alpha/beta interferon producti

60 phosphorylation and nuclear translocation of IRF-3 and an increased promoter binding activity for IRF

61 poptotic transcription factors NF-kappaB and IRF-3 and elicit apoptosis.

62 Rather, PLpro interacts with IRF-3 and inhibits the phosphorylation and nuclear trans

63 onded to paramyxovirus infection to activate IRF-3 and interferon-stimulated gene expression, but the

64 However, both IRF-3 and IRF-7 are critical for the production of type

65 In this study, we demonstrate that IRF-3 and IRF-7 are functionally redundant, but lack of

66 /beta response; only the combined actions of IRF-3 and IRF-7 are necessary for efficient control of e

67 Collectively, these results demonstrate that IRF-3 and IRF-7 are redundant, albeit IRF-7 plays a more

68 Interferon regulatory factors IRF-3 and IRF-7 are transcription factors essential in t

69 bers, we have solved the X-ray structures of IRF-3 and IRF-7 DBDs in the absence of DNA.

70 The X-ray structures of IRF-3 and IRF-7 DNA binding domains (DBDs) bound to IFN-

71 2 were rapidly induced independently of both IRF-3 and IRF-7 in the Irf-3(-/-)7(-/-) mice with DENV i

72 IRF-3 and IRF-7 restrict MNV replication in both culture

73 In mice, deletion of IFNAR, MAVS, or IRF-3 and IRF-7 resulted in uncontrolled OROV replicatio

74 Interestingly, redundancy of IRF-3 and IRF-7 was age dependent, as neonatal animals l

75 more, we show that the transcription factors IRF-3 and IRF-7 work in concert to initiate unique and o

76 luding interferon regulatory factor 3 and 7 (IRF-3 and IRF-7) and STAT-1, suggesting that neuronal ma

77 tablish a dominant protective role for MAVS, IRF-3 and IRF-7, and IFNAR in restricting OROV infection

78 cularly the regulatory transcription factors IRF-3 and IRF-7, have key protective roles during OROV i

79 utrophils and dendritic cells, as well as of IRF-3 and IRF-7, is critical for innate immune responses

80 ng MAVS signaling, the transcription factors IRF-3 and IRF-7, or IFNAR than in wild-type (WT) cells.

81 action partners, including their substrates, IRF-3 and IRF-7.

82 exes directs IRF-3 phosphorylation, and both IRF-3 and NF-kappaB activation are required for transcri

83 ly protein of the Bcl-2 family that requires IRF-3 and NF-kappaB for efficient expression.

84 for apoptosis, nor have the genes induced by IRF-3 and NF-kappaB that are responsible for apoptosis b

85 is essential for blocking RIG-I signaling to IRF-3 and NF-kappaB, whereas the helicase domain is disp

86 is mediated directly by genes responsive to IRF-3 and NF-kappaB.

87 d an increased promoter binding activity for IRF-3 and NF-kappaB.

88 reovirus infection in a manner dependent on IRF-3 and NF-kappaB.

89 oma cells led to impaired phosphorylation of IRF-3 and reduced ubiquitination of RIG-I and TBK-1, whi

90 l interfering RNAs blocked the activation of IRF-3 and subsequent IFN-alpha/beta production induced b

91 irus strains achieved similar peak titers in IRF-3(+/+) and IRF-3(-/-) mice in the intestine, brain,

92 F-3 in reovirus disease, we infected newborn IRF-3(+/+) and IRF-3(-/-) mice perorally with mildly vir

93 IRF-3(-/-) and select IRF-3/7(-/-) mice were resistant t

94 tion factors interferon regulatory factor-3 (IRF-3) and NF-kappaB, resulting in secretion of the anti

95 tion factors interferon regulatory factor 3 (IRF-3) and nuclear factor kappa light-chain enhancer of

96 ctivation of interferon regulatory factor-3 (IRF-3) and nuclear factor kappaB (NF-kappaB) through the

97 iption factors, the IFN regulatory factor 3 (IRF-3) and nuclear factor kappaB (NF-kappaB), as evidenc

98 ctivation of interferon regulatory factor 3 (IRF-3) and synthesis of type 1 interferons (IFN-alpha/be

99 tor (CIITA), interferon regulatory factor 3 (IRF-3), and interferon regulatory factor 7 (IRF-7) were

100 promoter, mediated nuclear translocation of IRF-3, and displayed highly potent activity against hepa

101 d the interferon regulatory factors (IRF)-1, IRF-3, and IRF-7 to the RANTES independently of myeloid

102 hMPV infection induces activation of IRF-3, and it regulates the expression of IRF-7.

103 In addition to IRF-3- and IFN-mediated antiviral responses, IFN-indepen

104 ntrol of early DENV infection; and the late, IRF-3- and IRF-7-independent pathway contributes to anti

105 Ifit1, Ifit3, and Mx2 can be induced via an IRF-3- and IRF-7-independent pathway that does not invol

106 e responses were equivalent in wild-type and IRF-3(-/-) animals, suggesting that IRF-3 functions inde

107 ption factor interferon regulatory factor 3 (IRF-3) are often vital for early pathogen control, and e

108 -kappaB) and interferon regulatory factor 3 (IRF-3) at a step subsequent to their nuclear translocati

109 Our results clearly demonstrate that the IRF-3/Bax-mediated apoptotic signaling branch contribute

110 increased transcription is due to increased IRF-3 binding to and transactivation of the TNF promoter

111 in the presence of exogenously supplied IFN, IRF-3(-/-) BMDCs are inherently defective in the control

112 However, while IFN pretreatment of IRF-3(-/-) BMDCs resulted in reduced virus titers, a far

113 In this study, HSV-1-infected IRF-3(-/-) bone marrow-derived dendritic cells (BMDCs) a

114 firmed by atomic force microscopy of dimeric IRF-3 bound to the PRDII-PRDI tandem recognition sites p

115 IKKepsilon or TBK-1 phosphorylates not only IRF-3 but also VP35.

116 h the DNA minor groove, is disordered in apo IRF-3 but is ordered in apo IRF-7.

117 sponse associated with a marked depletion of IRF-3 but not IRF-7 in HIV-1-infected cells, which suppo

118 -708 phosphorylation occurs independently of IRF-3 but requires signaling through the IFN-alpha/beta

119 ough to drive the transcriptional effects of IRF-3 but too low to trigger its apoptotic activity.

120 iption induction by IFN regulatory factor 3 (IRF-3) but do so at different points in the signaling pa

121 FN-I expression was found to be dependent on IRF-3, but not NF-kappaB.

122 itination of two specific lysine residues of IRF-3 by LUBAC, the linear polyubiquitinating enzyme com

123 orylation of interferon regulatory factor 3 (IRF-3) by the Ebola VP35 protein may block the host inna

124 nce that innate immune pathways dependent on IRF-3 can be successfully targeted by small-molecule dru

125 ay activates the latent transcription factor IRF-3, causing its nuclear translocation and the inducti

126 -kappaB) and interferon regulatory factor 3 (IRF-3), classically inducing IFNbeta production.

127 sults demonstrated that in our model system, IRF-3 controlled the fate of the SeV-infected cells by p

128 transcriptionally inert; this single-action IRF-3 could protect mice from lethal viral infection.

129 In addition, IRF-3-deficient BMDCs exhibited delayed type I IFN synth

130 wild-type mice survived, compared to 10% of IRF-3-deficient mice.

131 espite the fact that all IL-33 agonists were IRF-3 dependent, LPS-induced IL-33 mRNA was fully induci

132 ascade, often in an IFN regulatory factor 3 (IRF-3)-dependent fashion.

133 on via interferon (IFN) regulatory factor 3 (IRF-3)-dependent pathways.

134 kinase-related kinases are implicated in the IRF-3-dependent antiviral response.

135 ut only if they can find a way to impair the IRF-3-dependent apoptotic pathway.

136 nd induction of interferon regulatory factor IRF-3-dependent gene transcription.

137 hanced restriction by type I interferon- and IRF-3-dependent mechanisms.

138 Furthermore, IRF-3-dependent neuronal protection from virus-mediated

139 occur through the activities of STAT-1- and IRF-3-dependent pathways and cannot be explained solely

140 0 by itself can interfere with interferon or IRF-3-dependent signaling and whether ICP0 enables the v

141 IRF-3 promotes HIV-1 infection by disrupting IRF-3-dependent signaling pathways and innate antiviral

142 Despite being partially controlled by IRF-3-dependent signals, WEEV also disrupted antiviral r

143 IRF-3 depletion was dependent on a productive HIV-1 repl

144 er binds only one full-length phosphomimetic IRF-3 dimer at the PRDIII-PRDI sites, and this binding d

145 In contrast, bound IRF-3 dimer interacts strongly with the NF-kappaB (p50/p

146 efore, not determined by the presence of the IRF-3 dimer, but is predetermined by the asymmetry of th

147 n reveals that the pLxIS motif also mediates IRF-3 dimerization and activation.

148 rylation at site 1 is, in turn, required for IRF-3 dimerization.

149 CBP also interacts in vitro with IRF-3 double-site mutants to form different levels of ol

150 The elevated levels of IRF-3-driven genes in the PI cells indicated that the am

151 ption factor interferon regulatory factor 3 (IRF-3) enhances reovirus-induced apoptosis following act

152 a tetracycline (Tet)-inducible cell line for IRF-3 expression, which enabled us to express various le

153 atory factor 7 (IRF-7) expression but not on IRF-3 expression.

154 cedented insight into negative regulation of IRF-3 following activation of the type I IFN antiviral r

155 l protein 1) employs a pLxIS motif to target IRF-3 for degradation, but phosphorylation of NSP1 is no

156 lication-dependent manner, and abrogation of IRF-3 function enhanced virus-mediated injury by WEEV an

157 lication-dependent manner, and abrogation of IRF-3 function enhanced virus-mediated injury by WEEV an

158 IRF-3 functions downstream of several viral sensors, inc

159 type and IRF-3(-/-) animals, suggesting that IRF-3 functions independently of the adaptive immune res

160 Mutation of a consensus cleavage site within IRF-3 generates a form that is not cleaved by caspase-8

161 lso show that caspase-8-mediated cleavage of IRF-3 helps to modulate dsRNA-dependent gene induction.

162 t and activation of the transcription factor IRF-3 (IFN regulatory factor 3).

163 over, VP35 overexpression impairs IKKepsilon-IRF-3, IKKepsilon-IRF-7, and IKKepsilon-IPS-1 interactio

164 hosphorylated STING, MAVS, and TRIF binds to IRF-3 in a similar manner, whereas residues upstream of

165 These data demonstrate a critical role for IRF-3 in control of central nervous system infection fol

166 activated phosphorylation of IKKepsilon and IRF-3 in FLS.

167 tients exhibited the nuclear, active form of IRF-3 in hepatocytes and an associated increase in IRF-3

168 lbeit IRF-7 plays a more important role than IRF-3 in inducing the initial IFN-alpha/beta response; o

169 To determine the role of IRF-3 in reovirus disease, we infected newborn IRF-3(+/+

170 lyubiquitinating enzyme complex, which bound IRF-3 in signal-dependent fashion.

171 Introduction of IRF-3 in the persistently infected cells restored the ce

172 onally, these agonists efficiently activated IRF-3 in the presence of the HCV protease NS3-4A, which

173 ntain kinase activity that can phosphorylate IRF-3 in vitro.

174 nase IKKepsilon and IFN regulatory factor 3 (IRF-3) in the activation of antiviral genes in rheumatoi

175 ent with a role for IFN regulatory factor-3 (IRF-3) in the expression of IL-33.

176 , we report a novel and distinct activity of IRF-3, in virus-infected cells, that induces apoptosis.

177 Here, we show that vIRF-2 mediates IRF-3 inactivation by a mechanism involving caspase-3, a

178 equent innate signaling cascades, activating IRF-3 independently of CD14.

179 es differ by only a single amino acid in the IRF-3 inhibitory domain of VP35, the level of alteration

180 cEbo-VP35/R312A) within a previously defined IRF-3 inhibitory domain.

181 exhibited various levels of translocation of IRF-3 into the nucleus.

182 , interferon regulatory factors (IRF) IRF-1, IRF-3, IRF-5, IRF-7, mitochondrial antiviral signaling m

183 Thus, IRF-3 is a dual-action cytoplasmic protein that, upon ac

184 represents a folded structural domain; i.e., IRF-3 is a three-domain globular protein.

185 Upon infection, host cell IRF-3 is activated by phosphorylation at its seven C-ter

186 As IRF-3 is downstream from the TLR4 adaptor TIR-domain-con

187 IRF-3 is targeted for proteasome-mediated degradation, w

188 ation of a stable dimer; (c) dimerization of IRF-3 is the basis of its strong binding to PRDIII-PRDI

189 Interferon regulatory factor 3 (IRF-3) is a key transcription factor in the assembly of

190 Interferon response factor 3 (IRF-3) is a transcription factor that plays an essential

191 interferon regulatory transcription factor (IRF-3) is activated by phosphorylation of Ser/Thr residu

192 Interferon regulatory factor 3 (IRF-3) is essential for innate intracellular immune defe

193 When IRF-3-knockdown cells were infected with Sendai virus (S

194 IRF-3 levels were reduced in vivo within CD4+ T cells fr

195 infected; although seven out of them had low IRF-3 levels, four did not.

196 y, induction of IL-33 mRNA was attenuated in IRF-3(-/-) macrophages and TBK-1(-/-) mouse embryonic fi

197 IRF-3 may direct an innate antiviral response that regul

198 Our observations indicated that IRF-3-mediated apoptosis of virus-infected cells could b

199 We found that WEEV activated IRF-3-mediated neuronal innate immune pathways in a repl

200 We found that WEEV activated IRF-3-mediated neuronal innate immune pathways in a repl

201 LR), which can also activate the RLR-induced IRF-3-mediated pathway of apoptosis (RIPA).

202 hese results demonstrate a critical role for IRF-3-mediated pathways in controlling HSV-1 replication

203 The transcription factor IRF-3 mediates cellular antiviral response by inducing t

204 ption factor interferon regulatory factor 3 (IRF-3), MHV did not induce IFN-beta protein production d

205 ontrast, the present study demonstrated that IRF-3(-/-) mice are significantly more susceptible to HS

206 production were observed in brain tissues of IRF-3(-/-) mice compared to control mice, with a concomi

207 n herpes simplex virus (HSV) pathogenesis in IRF-3(-/-) mice following intravenous HSV type 1 (HSV-1)

208 hieved similar peak titers in IRF-3(+/+) and IRF-3(-/-) mice in the intestine, brain, heart, liver, a

209 disease, we infected newborn IRF-3(+/+) and IRF-3(-/-) mice perorally with mildly virulent strain ty

210 /beta was induced similarly in wild-type and Irf-3(-/-) mice post-DENV infection, whereas in the Irf-

211 Both wild-type and IRF-3(-/-) mice succumbed with equivalent frequencies to

212 gans examined were 10- to 100-fold higher in IRF-3(-/-) mice than those in wild-type mice.

213 Bending of DNA by IRF-3 must be significant in the assembly and function o

214 More importantly, transcriptionally inactive IRF-3 mutants, such as the one missing its DNA-binding d

215 anced activation of IFN regulatory factor 3 (IRF-3), NF-kappaB, and ATF-2 in C(ko)-infected compared

216 ithout altering the nuclear translocation of IRF-3 or IFN-beta mRNA production or stability.

217 ciprocal bone marrow chimeras indicated that IRF-3 or IRF-7 expression in either hematopoietic or non

218 downstream regulatory transcription factors (IRF-3 or IRF-7), beta interferon (IFN-beta), or the rece

219 n is sufficient for interactions with either IRF-3 or VP35.

220 c-Jun N-terminal kinase (JNK), but not p38, IRF-3, or NF-kappaB.

221 These data demonstrate that the Trif/IRF-3 pathway is a target to ameliorate liver dysfunctio

222 set by DA L as well as other factors in the IRF-3 pathway may play a role in virus persistence, infl

223 r, the role of each phosphorylation site for IRF-3 phosphoactivation remains unresolved.

224 6 serve antagonistic functions in regulating IRF-3 phosphoactivation.

225 The structure of the IRF-3 phosphomimetic mutant S386/396E bound to the cAMP

226 Both IRF-3 phosphorylation and cell apoptosis induced by infe

227 DN IKKepsilon inhibited IRF-3 phosphorylation as well as RANTES and IFNbeta prot

228 ction at 39 degrees C, induced PKR-dependent IRF-3 phosphorylation at 39 degrees C but not at 31 degr

229 he formation of TBK1-TRAF3 complexes directs IRF-3 phosphorylation, and both IRF-3 and NF-kappaB acti

230 inhibited rhinovirus-induced IFN production, IRF-3 phosphorylation, and IKKepsilon expression and inh

231 RIG-I in pancreatic carcinoma cells induced IRF-3 phosphorylation, production of type I IFN, the che

232 l responses resulting from the inhibition of IRF-3 phosphorylation.

233 er STAT1 nor interferon regulatory factor 3 (IRF-3) play essential roles in the replication defect of

234 Interferon regulatory factor 3 (IRF-3) plays a central role in inducing the expression o

235 r results indicate that viral suppression of IRF-3 promotes HIV-1 infection by disrupting IRF-3-depen

236 Transcription from an IRF-3-responsive promoter was partially inhibited by MHV

237 d, especially in the heart, where absence of IRF-3 resulted in severe myocarditis.

238 stricting infection and that a deficiency of IRF-3 results in enhanced lethality.

239 dues, which increases the negative charge of IRF-3, results in its dimerization and association with

240 In RNA-virus infected cells, IRF-3's transcriptional activation is triggered primaril

241 Independent of IRF-3's transcriptional role, a novel IRF-3 activation p

242 In contrast, IRF-3 S385D weakened the interaction and oligomerization

243 Although IRF-3 S386D alone did not interact as strongly with CBP

244 kened the interaction and oligomerization of IRF-3 S396D and S386/396D with CBP.

245 Among all the single-site mutants, IRF-3 S396D showed the strongest binding to CBP.

246 hened the interaction and oligomerization of IRF-3 S396D with CBP.

247 rm heterodimers, but when CBP interacts with IRF-3 S396D, oligomerization is evident.

248 Thus, IRF-3 serves to facilitate virus clearance and prevent t

249 ATF-2 or SMAD-3, but not IRF-3, short-hairpin RNA reduced p19 promoter activity a

250 Mice lacking IFN regulatory factor 3 (IRF-3) show increased vulnerability to WNV infection wit

251 Light scattering studies of wild-type IRF-3 showed that these three domains are tightly packed

252 study quantitatively assessed the rescue of IRF-3 signaling by NS3/4A inhibitors, compared with in v

253 NS3/4A protease inhibitors can restore IRF-3 signaling in HCV-infected cells but only at concen

254 A sensor, which is required for induction of IRF-3 signaling in these cells, is nuclear, and its loca

255 IFN-alpha/beta through the activation of the IRF-3 signaling pathway.

256 ization and degradation of IFI16, inhibiting IRF-3 signaling.

257 y upon HSV-1 d109 infection and induction of IRF-3 signaling.

258 al DNA release from incoming capsids inhibit IRF-3 signaling.

259 echanisms of interferon regulatory factor-3 (IRF-3) signaling in primary human foreskin fibroblasts (

260 (TBK1)-interferon (IFN) regulatory factor 3 (IRF-3) signaling pathway.

261 Deletions upstream from the IRF-3 site and mutations at the IRF-3, SMAD-3, ATF-2, or

262 eam from the IRF-3 site and mutations at the IRF-3, SMAD-3, ATF-2, or NF-kappaB, but not the IRF-7, s

263 cation, whereas ectopic expression of active IRF-3 suppressed HIV-1 infection.

264 manner dependent on IFN regulatory factor 3 (IRF-3), TANK-binding kinase 1 (TBK1) and stimulator of i

265 in hepatocytes and an associated increase in IRF-3 target gene expression in hepatic tissue.

266 tatus of IRF-3 activation, and expression of IRF-3 target genes and ISGs during asynchronous HCV infe

267 hanism for the recruitment and activation of IRF-3 that can be subverted by viral proteins to evade i

268 lly targeted mouse, which expressed a mutant IRF-3 that was RIPA-competent but transcriptionally iner

269 Thus, in intact IRF-3, the linker represents a folded structural domain;

270 F-kappaB and interferon regulatory factor 3 (IRF-3), thereby inducing the synthesis of proinflammator

271 phosphorylation and nuclear translocation of IRF-3, thereby disrupting the activation of type I IFN r

272 However, it was not clear whether in intact IRF-3 this linker segment of the chain, which carries th

273 We confirmed this IRF-3 threshold idea by generating a tetracycline (Tet)-

274 nducing IFN-beta) mediate the recruitment of IRF-3 through a conserved pLxIS motif.

275 ust be exported from the nucleus to activate IRF-3 through cytoplasmic STING, which is required for I

276 to induce the transcriptional activation of IRF-3 through the TLR4/MD2-dependent pathway.

277 s was triggered by the direct interaction of IRF-3, through a newly identified BH3 domain, with the p

278 The ability of IRF-3 to bind these variable sites derives in part from

279 This phosphoactivation triggers IRF-3 to react with the coactivators, CREB-binding prote

280 tics of binding of the monomeric and dimeric IRF-3 to the enhancer DNA indeed showed that formation o

281 Translocation of IRF-3 to the nucleus was observed beginning at 8 h, IRF-

282 ting the ability of IFN regulatory factor 3 (IRF-3) to function as a transcription factor.

283 ivation of the interferon regulatory factor (IRF-3) transcription factor.

284 Activated IRF-3 translocates to the nucleus and initiates the tran

285 o show that caspase-3 participates in normal IRF-3 turnover in the absence of vIRF-2, during the anti

286 Interferon regulatory factor 3 (IRF-3) undergoes phosphorylation-induced activation in v

287 When IRF-3 was absent or its activation by the RIG-I pathway

288 However, the absence of IRF-3 was associated with significantly decreased surviv

289 However, IRF-3 was not required for optimal systemic IFN producti

290 nduction of the proapototic protein TRAIL by IRF-3 was not required.

291 ultiple cells types (e.g. A549, P388D1), and IRF-3 was not translocated to the nucleus in TCRV-infect

292 ter was partially inhibited by MHV; however, IRF-3 was transported to the nucleus and bound DNA in MH

293 phosphorylation and nuclear accumulation of IRF-3 were detected in PKR-sufficient cells following in

294 orylation of interferon regulatory factor 3 (IRF-3), which is the key transcription factor for IFN in

295 s pathway is interferon regulatory factor 3 (IRF-3), which upon activation by virus infection binds B

296 tightly packed, and therefore, the dimer of IRF-3, which is formed upon phosphorylation of its C-ter

297 , the nuclear accumulation of phosphorylated IRF-3, which is necessary for the induction of type I IF

298 Dimerization of the transcription factor IRF-3, which is required for synthesis of IFN-beta mRNA,

299 The absence of IRF-3 would be expected to render such pathways inoperat

300 This dependence predicts that loss of IRF-3 would render early recognition pathways inoperativ