scholarly journals Regulation of Type I Interferon Gene Expression by Interferon Regulatory Factor-3

1998 ◽  
Vol 273 (5) ◽  
pp. 2714-2720 ◽  
Author(s):  
Susan L. Schafer ◽  
Rongtuan Lin ◽  
Paul A. Moore ◽  
John Hiscott ◽  
Paula M. Pitha
Keyword(s):  
Gene Expression ◽  
Type I Interferon ◽  
Interferon Regulatory Factor ◽  
Type I ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 3 ◽  
Interferon Gene

scholarly journals The 3C Protein of Enterovirus 71 Inhibits Retinoid Acid-Inducible Gene I-Mediated Interferon Regulatory Factor 3 Activation and Type I Interferon Responses

2010 ◽  
Vol 84 (16) ◽  
pp. 8051-8061 ◽  
Author(s):  
Xiaobo Lei ◽  
Xinlei Liu ◽  
Yijie Ma ◽  
Zhenmin Sun ◽  
Yaowu Yang ◽  
...  
Keyword(s):  
Rna Binding ◽  
Type I Interferon ◽  
Critical Role ◽  
Enterovirus 71 ◽  
Interferon Regulatory Factor ◽  
Type I ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 3 ◽  
Retinoid Acid ◽  
Inducible Gene

ABSTRACT Enterovirus 71 (EV71) is a human pathogen that induces hand, foot, and mouth disease and fatal neurological diseases. Immature or impaired immunity is thought to associate with increased morbidity and mortality. In a murine model, EV71 does not facilitate the production of type I interferon (IFN) that plays a critical role in the first-line defense against viral infection. Administration of a neutralizing antibody to IFN-α/β exacerbates the virus-induced disease. However, the molecular events governing this process remain elusive. Here, we report that EV71 suppresses the induction of antiviral immunity by targeting the cytosolic receptor retinoid acid-inducible gene I (RIG-I). In infected cells, EV71 inhibits the expression of IFN-β, IFN-stimulated gene 54 (ISG54), ISG56, and tumor necrosis factor alpha. Among structural and nonstructural proteins encoded by EV71, the 3C protein is capable of inhibiting IFN-β activation by virus and RIG-I. Nevertheless, EV71 3C exhibits no inhibitory activity on MDA5. Remarkably, when expressed in mammalian cells, EV71 3C associates with RIG-I via the caspase recruitment domain. This precludes the recruitment of an adaptor IPS-1 by RIG-I and subsequent nuclear translocation of interferon regulatory factor 3. An R84Q or V154S substitution in the RNA binding motifs has no effect. An H40D substitution is detrimental, but the protease activity associated with 3C is dispensable. Together, these results suggest that inhibition of RIG-I-mediated type I IFN responses by the 3C protein may contribute to the pathogenesis of EV71 infection.

scholarly journals The Lyme Disease Spirochete Borrelia burgdorferi Utilizes Multiple Ligands, Including RNA, for Interferon Regulatory Factor 3-Dependent Induction of Type I Interferon-Responsive Genes

2010 ◽  
Vol 78 (7) ◽  
pp. 3144-3153 ◽  
Author(s):  
Jennifer C. Miller ◽  
Heather Maylor-Hagen ◽  
Ying Ma ◽  
John H. Weis ◽  
Janis J. Weis
Keyword(s):  
Borrelia Burgdorferi ◽  
Gene Transcription ◽  
Type I Interferon ◽  
Interferon Regulatory Factor ◽  
Lyme Arthritis ◽  
Type I ◽  
Type I Ifn ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 3 ◽  
Responsive Gene

ABSTRACT We recently discovered a critical role for type I interferon (IFN) in the development of murine Lyme arthritis. Borrelia burgdorferi-mediated induction of IFN-responsive genes by bone marrow-derived macrophages (BMDMs) was dependent upon a functional type I IFN receptor but independent of Toll-like receptor 2 (TLR2), TLR4, TLR9, and the adapter molecule MyD88. We now demonstrate that induction of the IFN transcriptional profile in B. burgdorferi-stimulated BMDMs occurs independently of the adapter TRIF and of the cytoplasmic sensor NOD2. In contrast, B. burgdorferi-induced transcription of these genes was dependent upon a rapid STAT1 feedback amplification pathway. IFN profile gene transcription was IRF3 dependent but did not utilize B. burgdorferi-derived DNA or DNase-sensitive ligands. Instead, IFN-responsive gene expression could be induced by B. burgdorferi-derived RNA. Interferon regulatory factor 3 (IRF3)-dependent IFN profile gene transcription was also induced by sonicated bacteria, by the lipoprotein OspA, and by factors released into the BSKII medium during culture of B. burgdorferi. The IFN-stimulatory activity of B. burgdorferi culture supernatants was not destroyed by nuclease treatment. Nuclease digestion also had no effect on IFN profile induction mediated by sonicated B. burgdorferi. Thus, B. burgdorferi-derived RNA, OspA, and non-nucleic acid ligands present in both sonicated bacteria and B. burgdorferi culture medium contribute to type I IFN-responsive gene induction. These findings suggest that B. burgdorferi invasion of joint tissue and the resultant type I IFN induction associated with Lyme arthritis development may involve multiple triggering ligands.

scholarly journals Human Rhinovirus Attenuates the Type I Interferon Response by Disrupting Activation of Interferon Regulatory Factor 3

2006 ◽  
Vol 80 (10) ◽  
pp. 5021-5031 ◽  
Author(s):  
Tao Peng ◽  
Swathi Kotla ◽  
Roger E. Bumgarner ◽  
Kurt E. Gustin
Keyword(s):  
Type I Interferon ◽  
Transcriptional Response ◽  
Interferon Regulatory Factor ◽  
Alveolar Epithelial Cells ◽  
Interferon Response ◽  
Type I ◽  
Regulatory Factor ◽  
Full Spectrum ◽  
Interferon Regulatory Factor 3 ◽  
Infected Cells

ABSTRACT The type I interferon (IFN) response requires the coordinated activation of the latent transcription factors NF-κB, interferon regulatory factor 3 (IRF-3), and ATF-2, which in turn activate transcription from the IFN-β promoter. Synthesis and subsequent secretion of IFN-β activate the Jak/STAT signaling pathway, resulting in the transcriptional induction of the full spectrum of antiviral gene products. We utilized high-density microarrays to examine the transcriptional response to rhinovirus type 14 (RV14) infection in HeLa cells, with particular emphasis on the type I interferon response and production of IFN-β. We found that, although RV14 infection results in altered levels of a wide variety of host mRNAs, induction of IFN-β mRNA or activation of the Jak/STAT pathway is not seen. Prior work has shown, and our results have confirmed, that NF-κB and ATF-2 are activated following infection. Since many viruses are known to target IRF-3 to inhibit the induction of IFN-β mRNA, we analyzed the status of IRF-3 in infected cells. IRF-3 was translocated to the nucleus and phosphorylated in RV14-infected cells. Despite this apparent activation, very little homodimerization of IRF-3 was evident following infection. Similar results in A549 lung alveolar epithelial cells demonstrated the biological relevance of these findings to RV14 pathogenesis. In addition, prior infection of cells with RV14 prevented the induction of IFN-β mRNA following treatment with double-stranded RNA, indicating that RV14 encodes an activity that specifically inhibits this innate host defense pathway. Collectively, these results indicate that RV14 infection inhibits the host type I interferon response by interfering with IRF-3 activation.

scholarly journals Opposing Roles for Interferon Regulatory Factor-3 (IRF-3) and Type I Interferon Signaling during Plague

2012 ◽  
Vol 8 (7) ◽  
pp. e1002817 ◽  
Author(s):  
Ami A. Patel ◽  
Hanni Lee-Lewis ◽  
Jennifer Hughes-Hanks ◽  
Craig A. Lewis ◽  
Deborah M. Anderson
Keyword(s):  
Type I Interferon ◽  
Interferon Regulatory Factor ◽  
Type I ◽  
Interferon Signaling ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 3
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