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Stimulator of interferon genes

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https://www.readbyqxmd.com/read/28922377/c-reactive-protein-upregulates-the-whole-blood-expression-of-cd59-an-integrative-analysis
#1
Kaido Lepik, Tarmo Annilo, Viktorija Kukuškina, Kai Kisand, Zoltán Kutalik, Pärt Peterson, Hedi Peterson
Elevated C-reactive protein (CRP) concentrations in the blood are associated with acute and chronic infections and inflammation. Nevertheless, the functional role of increased CRP in multiple bacterial and viral infections as well as in chronic inflammatory diseases remains unclear. Here, we studied the relationship between CRP and gene expression levels in the blood in 491 individuals from the Estonian Biobank cohort, to elucidate the role of CRP in these inflammatory mechanisms. As a result, we identified a set of 1,614 genes associated with changes in CRP levels with a high proportion of interferon-stimulated genes...
September 18, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28921470/cgas-sting-activation-in-the-tumor-microenvironment-and-its-role-in-cancer-immunity
#2
Geneviève Pépin, Michael P Gantier
Stimulator of interferon (IFN) genes (STING) is a key mediator in the immune response to cytoplasmic DNA sensed by cyclic GMP-AMP (cGAMP) synthase (cGAS). After synthesis by cGAS, cGAMP acts as a second messenger activating STING in the cell harboring cytoplasmic DNA but also in adjacent cells through gap junction transfer. While the role of the cGAS-STING pathway in pathogen detection is now well established, its importance in cancer immunity has only recently started to emerge. Nonetheless, STING appears to be an essential component in the recruitment of immune cells to the tumor microenvironment, which is paramount to immune clearance of the tumor...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28916184/role-of-the-il-12-il-35-balance-in-sj%C3%A3-gren-s-syndrome
#3
Olivier Fogel, Elodie Rivière, Raphaèle Seror, Gaetane Nocturne, Saida Boudaoud, Bineta Ly, Jacques-Eric Gottenberg, Véronique Le Guern, Jean-Jacques Dubost, Joanne Nititham, Kimberly E Taylor, Philippe Chanson, Philippe Dieudé, Lindsey A Criswell, Bernd Jagla, Alice Thai, Michael Mingueneau, Xavier Mariette, Corinne Miceli-Richard
BACKGROUND: An interferon (IFN) signature is involved in the pathogenesis of primary Sjögren's syndrome (pSS), but whether the signature is type 1 or 2 remains controversial. Mouse models and genetic studies suggested the involvement of T helper 1 and type 2 IFN pathways. Likewise, polymorphisms of interleukin 12A gene (IL-12A), which encodes for IL-12p35, have been associated with pSS. IL-12p35 subunit is shared by 2 heterodimers, IL-12 and IL-35. OBJECTIVE: To confirm the genetic association of IL-12A polymorphism and pSS and elucidate the involvement of the IL-12/IL-35 balance in pSS by functional studies...
September 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28913576/interferon-activates-promoter-of-nmi-gene-via-interferon-regulator-factor-1
#4
Xiao Xu, Keli Chai, Yuhang Chen, Yongquan Lin, Suzhen Zhang, Xin Li, Wentao Qiao, Juan Tan
N-Myc interactor (Nmi) is reported to participate in many activities, such as signaling transduction, transcription regulation, and antiviral responses. As Nmi may play important roles in interferon (IFN)-induced responses, we investigated the mechanism how Nmi protein is regulated. We identified and cloned the promoter of Nmi gene. Sequence analysis and luciferase assays shown that an IFN-stimulated response element (ISRE) and a GC box in the promoter were essential for the basal transcription activity of Nmi gene...
September 14, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28912382/versican-is-produced-by-trif-and-type-i-interferon-dependent-signaling-in-macrophages-and-contributes-to-fine-control-of-innate-immunity-in-lungs
#5
Mary Y Chang, Inkyung Kang, Michael Gale, Anne M Manicone, Michael G Kinsella, Kathleen R Braun, Tara Wigmosta, William C Parks, William A Altemeier, Thomas N Wight, Charles W Frevert
Growing evidence suggests that versican is important in the innate immune response to lung infection. Our goal was to understand the regulation of macrophage-derived versican and the role it plays in innate immunity. We first defined the signaling events that regulate versican expression using bone marrow derived macrophages (BMDM) from mice lacking specific Toll-like receptors (TLR), TLR adaptor molecules or the type I interferon receptor (IFNAR1). We show that LPS and polyinosinic-polycytidylic acid [Poly(I:C)] trigger a signaling cascade involving TLR3 or 4, the Trif adaptor, Type I interferons and IFNAR1, leading to increased expression of versican by macrophages and implicating versican as an interferon-stimulated gene...
September 14, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28910400/293texosome-mediated-mir-146a-transfer-suppresses-type-i-interferon-response-and-facilitates-ev71-infection
#6
Yuxuan Fu, Li Zhang, Fang Zhang, Ting Tang, Qi Zhou, Chunhong Feng, Yu Jin, Zhiwei Wu
Exosomes can transfer genetic materials between cells. Their roles in viral infections are beginning to be appreciated. Researches have shown that exosomes released from virus-infected cells contain a variety of viral and host cellular factors that are able to modulate recipient's cellular response and result in productive infection of the recipient host. Here, we showed that EV71 infection resulted in upregulated exosome secretion and differential packaging of the viral genomic RNA and miR-146a into exosomes...
September 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28910320/differential-gene-expression-following-tlr-stimulation-in-rag1-mutant-zebrafish-tissues-and-morphological-descriptions-of-lymphocyte-like-cell-populations
#7
Preeti J Muire, Larry A Hanson, Robert Wills, Lora Petrie-Hanson
In the absence of lymphocytes, rag1-/- mutant zebrafish develop protective immunity to bacteria. In mammals, induction of protection by innate immunity can be mediated by macrophages or natural killer (NK) cells. To elucidate potential responsive cell populations, we morphologically characterized lymphocyte-like cells (LLCs) from liver, spleen and kidney hematopoietic tissues. In fish, these cells include NK cells and Non-specific cytotoxic cells (NCCs). We also evaluated the transcriptional expression response of select genes that are important indicators of NK and macrophage activation after exposure to specific TLR ligands...
2017: PloS One
https://www.readbyqxmd.com/read/28900038/socs1-is-an-inducible-negative-regulator-of-ifn-lambda-induced-gene-expression-in-vivo
#8
Tanja Blumer, Mairene Coto-Llerena, Francois H T Duong, Markus H Heim
Type I (α and β) and type III (λ) interferons (IFNs) are induced upon viral infection through host sensory pathways that activate IFN regulatory factors (IRFs) and nuclear factor κB. Secreted IFNs induce autocrine and paracrine signalling through the JAK-Stat pathway leading to the transcriptional induction of hundreds of IFN stimulated genes (ISGs), amongst them sensory pathway components such as cGAS, STING, RIG-I, MDA5 and the transcription factor IRF7 that enhance the induction of IFNαs and IFNλss...
September 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28899396/transcriptomic-meta-analysis-identifies-gene-expression-characteristics-in-various-samples-of-hiv-infected-patients-with-nonprogressive-disease
#9
Le-Le Zhang, Zi-Ning Zhang, Xian Wu, Yong-Jun Jiang, Ya-Jing Fu, Hong Shang
BACKGROUND: A small proportion of HIV-infected patients remain clinically and/or immunologically stable for years, including elite controllers (ECs) who have undetectable viremia (<50 copies/ml) and long-term nonprogressors (LTNPs) who maintain normal CD4(+) T cell counts for prolonged periods (>10 years). However, the mechanism of nonprogression needs to be further resolved. In this study, a transcriptome meta-analysis was performed on nonprogressor and progressor microarray data to identify differential transcriptome pathways and potential biomarkers...
September 12, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28893653/hepatitis-c-virus-induced-innate-immune-responses-in-human-ips-cell-derived-hepatocyte-like-cells
#10
Fuminori Sakurai, Takemaru Kunito, Kazuo Takayama, Rina Hashimoto, Masashi Tachibana, Naoya Sakamoto, Takaji Wakita, Hiroyuki Mizuguchi
Hepatitis C virus (HCV) infection is a major cause of liver-related morbidity and mortality. In order to develop effective remedies for hepatitis C, it is important to understand the HCV infection profile and host-HCV interaction. HCV-induced innate immune responses play a crucial role in spontaneous HCV clearance; however, HCV-induced innate immune responses have not been fully evaluated in hepatocytes, partly because there are few in vitro models of HCV-induced innate immunity. Recently, human induced pluripotent stem (iPS) cells have received much attention as an in vitro model of infection with various pathogens, including HCV...
September 9, 2017: Virus Research
https://www.readbyqxmd.com/read/28890139/duck-interferon-regulatory-factor-1-acts-as-a-positive-regulator-in-duck-innate-antiviral-response
#11
Wei Qian, Xiaoqin Wei, Yongtao Li, Kelei Guo, Zhong Zou, Hongbo Zhou, Meilin Jin
In mammals, IFN regulatory factor (IRF) 1 can activates cellular genes and promotes viral resistance against some DNA and RNA viruses. Most IRFs have been identified as critical regulators in the IFN responses in both mammals and fish. In ducks, however, the functional role of IRF1 remains unknown. Here, we identified duck IRF1 (duIRF1) is essential to counteract viral invasion. duIRF1 is most abundant in duck spleen, and virus infection or poly(I:C) stimulation significantly induced duIRF1 expression in vivo and in vitro...
September 7, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28889286/detection-of-cyclic-dinucleotides-by-sting
#12
Xiao-Xia Du, Xiao-Dong Su
STING (stimulator of interferon genes) is an essential signaling adaptor protein mediating cytosolic DNA-induced innate immunity for both microbial invasion and self-DNA leakage. STING is also a direct receptor for cytosolic cyclic dinucleotides (CDNs), including the microbial secondary messengers c-di-GMP (3',3'-cyclic di-GMP), 3',3'cGAMP (3',3'-cyclic GMP-AMP), and mammalian endogenous 2',3'cGAMP (2',3'-cyclic GMP-AMP) synthesized by cGAS (cyclic GMP-AMP synthase). Upon CDN binding, STING undergoes a conformational change to enable signal transduction by phosphorylation and finally to active IRF3 (Interferon regulatory factor 3) for type I interferon production...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28888122/interferon-%C3%AF-induced-gene-expression-in-bovine-hepatocytes-during-early-pregnancy
#13
B Ruhmann, K Giller, A K Hankele, S E Ulbrich, M Schmicke
Interferon-tau (IFNτ) is the conceptus derived specific early pregnancy signal in bovidae. Locally, IFNτ induces an IFNτ specific gene expression (ISG) in endometrial cells and by this it averts luteolysis of the corpus luteum (CL) by suppressing prostaglandin production. Moreover, it was shown that IFNτ also induces ISG in the liver in pregnant sheep and in liver biopsies from Holstein Friesian heifers on Day 18 of pregnancy. The objective of the present study was to confirm increased hepatic ISG in vivo on Day 18 of pregnancy and to prove if hepatocytes and not non-parenchymal cells react to IFNτ by using immunohistochemistry and primary bovine hepatocytes stimulated in vitro with recombinant bovine IFNτ...
July 31, 2017: Theriogenology
https://www.readbyqxmd.com/read/28881486/how-usp18-deals-with-isg15-modified-proteins-structural-basis-for-the-specificity-of-the-protease
#14
REVIEW
Anja Basters, Klaus-Peter Knobeloch, Günter Fritz
The Ubiquitin-specific protease 18 (USP18) has two major functions: (i) it is a highly specific protease that cleaves the ubiquitin-like modifier ISG15 (interferon stimulated gene 15 kDa) from proteins, and (ii) independent from its enzymatic activity USP18 interacts with the type I interferon receptor and shuts off downstream signaling. The structures of USP18 and a USP18-ISG15 complex revealed the molecular basis of the unique specificity of the protease and might shed some light into its interaction with the interferon receptor...
September 7, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28878774/goose-mx-and-oasl-play-vital-roles-in-the-antiviral-effects-of-type-i-ii-and-iii-interferon-against-newly-emerging-avian-flavivirus
#15
Shun Chen, Wei Zhang, Zhen Wu, Jinyue Zhang, Mingshu Wang, Renyong Jia, Dekang Zhu, Mafeng Liu, Kunfeng Sun, Qiao Yang, Ying Wu, Xiaoyue Chen, Anchun Cheng
Duck Tembusu virus (TMUV), an emerging avian flavivirus, is highly pathogenic to birds and has the potential to become a zoonotic pathogen. Here, the molecular antiviral mechanism of goose type I, II, and III interferon (goIFNα, goIFNγ, and goIFNλ), the key components of the innate immune pathway, against TMUV was studied. We found that the transcription of goIFNs was obviously driven by TMUV infection in vivo and in vitro, and the titers and copies of TMUV were significantly reduced following treatment with goIFNs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28878077/irf9-prevents-cd8-t-cell-exhaustion-in-an-extrinsic-manner-during-acute-lcmv-infection
#16
Magdalena Huber, Tamara Suprunenko, Thomas Ashhurst, Felix Marbach, Hartmann Raifer, Svenja Wolff, Thomas Strecker, Barney Viengkhou, So Ri Jung, Hannah-Lena Obermann, Stefan Bauer, Haifeng C Xu, Philipp Lang, Adomati Tom, Karl S Lang, Nicholas J C King, Iain L Campbell, Markus J Hofer
Effective CD8(+) T cell responses play an important role in determining the course of a viral infection. Overwhelming antigen exposure can result in suboptimal CD8(+) T cell responses, leading to chronic infection. This altered CD8(+) T cell differentiation state, termed exhaustion, is characterized by reduced effector function, upregulation of inhibitory receptors and altered expression of transcription factors. Prevention of overwhelming antigen exposure which limits CD8(+) T cell exhaustion is of significant interest for controlling chronic infection...
September 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28877647/improvement-of-in-vivo-expression-of-genes-delivered-by-self-amplifying-rna-using-vaccinia-virus-immune-evasion-proteins
#17
Tim Beissert, Lars Koste, Mario Perkovic, Kerstin C Walzer, Stephanie Erbar, Abderaouf Selmi, Mustafa Diken, Sebastian Kreiter, Özlem Türeci, Ugur Sahin
Among nucleic acid based delivery platforms, self-amplifying RNA (saRNA) vectors are of increasing interest for applications such as transient expression of recombinant proteins and vaccination. saRNA is safe and, due to its capability to amplify intracellularly high protein levels, can by produced from even minute amounts of transfected templates. It is an obstacle to full exploitation of this platform, though, that saRNA induces a strong innate host immune response. In transfected cells pattern recognition receptors sense double-stranded RNA intermediates and via activation of protein kinase R (PKR) and interferon signaling initiate host defense measures including a translational shut-down...
September 6, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28877473/crimean-congo-hemorrhagic-fever-virus-suppresses-innate-immune-responses-via-a-ubiquitin-and-isg15-specific-protease
#18
Florine E M Scholte, Marko Zivcec, John V Dzimianski, Michelle K Deaton, Jessica R Spengler, Stephen R Welch, Stuart T Nichol, Scott D Pegan, Christina F Spiropoulou, Éric Bergeron
Antiviral responses are regulated by conjugation of ubiquitin (Ub) and interferon-stimulated gene 15 (ISG15) to proteins. Certain classes of viruses encode Ub- or ISG15-specific proteases belonging to the ovarian tumor (OTU) superfamily. Their activity is thought to suppress cellular immune responses, but studies demonstrating the function of viral OTU proteases during infection are lacking. Crimean-Congo hemorrhagic fever virus (CCHFV, family Nairoviridae) is a highly pathogenic human virus that encodes an OTU with both deubiquitinase and deISGylase activity as part of the viral RNA polymerase...
September 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28871935/topical-imiquimod-is-an-effective-and-safe-drug-for-molluscum-contagiosum-in-children
#19
George Badavanis, Efstathia Pasmatzi, Alexandra Monastirli, Sophia Georgiou, Dionysios Tsambaos
Dear Editor, Molluscum contagiosum (MC) is a very common skin infection caused by a molluscipox virus gene of the poxvirus family. It usually occurs in young children, sexually active adults, and immunocompromised individuals. The typical clinical picture of this infection is characterized by asymptomatic flesh-colored, single or multiple papules, measuring 2-6 mm in diameter with a central umbilication that occur on the skin and the mucous membranes. In adults, the skin lesions are predominantly located in the genital region, whereas in children they are found on the trunk, the extremities, and the face...
July 2017: Acta Dermatovenerologica Croatica: ADC
https://www.readbyqxmd.com/read/28870857/molecular-characterization-and-expression-analysis-of-interferon-gamma-in-black-seabream-acanthopagrus-schlegelii
#20
Yangxi Xiang, Wei Liu, Peng Jia, Yunlong Li, Yilin Jin, Limin Chen, Jing Zhang, Kuntong Jia, Meisheng Yi
Interferon gamma (IFN-γ) is a major component in immunological signaling and plays a key role in resisting viral infection. In this study, we identified and characterized an IFN-γ gene (AsIFN-γ) in the marine fish black seabream (Acanthopagrus schlegelii). We cloned AsIFN-γ genomic sequence, which comprises four exons, three introns and an upstream promoter including several conserved regulatory elements. The complete cDNA of AsIFN-γ was 816 bp in length and encoded a putative 194 amino acids (aa) protein with a 22 aa signal peptide, six α-helices and one nuclear localization signal (NLS)...
September 7, 2017: Fish & Shellfish Immunology
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