The CrkL Adapter Protein Is Required for Type I Interferon-Dependent Gene Transcription and Activation of the Small G-Protein Rap1

2002 ◽  
Vol 291 (4) ◽  
pp. 744-750 ◽  
Author(s):  
Fatima Lekmine ◽  
Antonella Sassano ◽  
Shahab Uddin ◽  
Beata Majchrzak ◽  
Osamu Miura ◽  
...  
Keyword(s):  
G Protein ◽  
Gene Transcription ◽  
Type I Interferon ◽  
Type I ◽  
Adapter Protein ◽  
Small G Protein

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 The VP3 Protein of Bluetongue Virus Associates with the MAVS Complex and Interferes with the RIG-I-Signaling Pathway

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 230
Author(s):  
Marie Pourcelot ◽  
Rayane Amaral Moraes ◽  
Aurore Fablet ◽  
Emmanuel Bréard ◽  
Corinne Sailleau ◽  
...  
Keyword(s):  
Bluetongue Virus ◽  
Type I Interferon ◽  
Type I ◽  
Adapter Protein ◽  
Structural Protein ◽  
Innate Response ◽  
Biting Midges ◽  
Domestic Ruminants ◽  
Infected Cells ◽  
Culicoides Biting Midges

Bluetongue virus (BTV), an arbovirus transmitted by Culicoides biting midges, is a major concern of wild and domestic ruminants. While BTV induces type I interferon (alpha/beta interferon [IFN-α/β]) production in infected cells, several reports have described evasion strategies elaborated by this virus to dampen this intrinsic, innate response. In the present study, we suggest that BTV VP3 is a new viral antagonist of the IFN-β synthesis. Indeed, using split luciferase and coprecipitation assays, we report an interaction between VP3 and both the mitochondrial adapter protein MAVS and the IRF3-kinase IKKε. Overall, this study describes a putative role for the BTV structural protein VP3 in the control of the antiviral response.

scholarly journals ABCC1/MRP1 exports cGAMP and modulates cGAS-dependent immunity

2021 ◽  
Author(s):  
Joanna H. Maltbaek ◽  
Jessica M. Snyder ◽  
Daniel B. Stetson
Keyword(s):  
Mouse Model ◽  
Cyclic Gmp ◽  
Regulatory Mechanism ◽  
Type I Interferon ◽  
Type I ◽  
Adapter Protein ◽  
Dna Sensor ◽  
Interferon Production ◽  
Sting Pathway ◽  
Cyclic Dinucleotide

AbstractThe DNA sensor cyclic GMP-AMP synthase (cGAS) is important for antiviral and anti-tumor immunity. cGAS generates cyclic GMP-AMP (cGAMP), a diffusible cyclic dinucleotide that activates the antiviral response through the adapter protein Stimulator of Interferon Genes (STING). cGAMP is negatively charged and cannot passively cross cell membranes, but recent advances have established a role for extracellular cGAMP as an “immunotransmitter” that can be imported into cells. However, the mechanism by which cGAMP exits cells remains unknown. Here, we identify ABCC1/MRP1 as an ATP-dependent cGAMP exporter that influences STING signaling and type I interferon production. We demonstrate that ABCC1 deficiency exacerbates cGAS-dependent autoimmunity in the Trex1-/- mouse model of Aicardi-Goutières syndrome. These studies identify ABCC1-mediated cGAMP export as a key regulatory mechanism of the cGAS-STING pathway.

scholarly journals Bclaf1 critically regulates the type I interferon response and is degraded by alphaherpesvirus US3

2018 ◽  
Author(s):  
Chao Qin ◽  
Rui Zhang ◽  
Yue Lang ◽  
Anwen Shao ◽  
Aotian Xu ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Pseudorabies Virus ◽  
Viral Infections ◽  
Type I Interferon ◽  
Interferon Response ◽  
Interferon Α ◽  
Type I ◽  
Viral Inhibition ◽  
Simplex Virus ◽  
Hsv 1

AbstractType I interferon response plays a prominent role against viral infection, which is frequently disrupted by viruses. Here, we report Bcl-2 associated transcription factor 1 (Bclaf1) is degraded during the alphaherpesvirus Pseudorabies virus (PRV) and Herpes simplex virus type 1 (HSV-1) infections through the viral protein US3. We further reveal that Bclaf1 functions critically in type I interferon signaling. Knockdown or knockout of Bclaf1 in cells significantly impairs interferon-α (IFNα)-mediated gene transcription and viral inhibition against US3 deficient PRV and HSV-1. Mechanistically, Bclaf1 maintains a mechanism allowing STAT1 and STAT2 to be efficiently phosphorylated in response to IFNα, and more importantly, facilitates IFN-stimulated gene factor 3 (ISGF3) binding with IFN-stimulated response elements (ISRE) for efficient gene transcription by directly interacting with ISRE and STAT2. Our studies establish the importance of Bclaf1 in IFNα-induced antiviral immunity and in the control of viral infections.

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