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type I interferon

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https://www.readbyqxmd.com/read/28640813/identification-of-a-sj%C3%A3-gren-s-syndrome-susceptibility-locus-at-oas1-that-influences-isoform-switching-protein-expression-and-responsiveness-to-type-i-interferons
#1
He Li, Tove Ragna Reksten, John A Ice, Jennifer A Kelly, Indra Adrianto, Astrid Rasmussen, Shaofeng Wang, Bo He, Kiely M Grundahl, Stuart B Glenn, Corinne Miceli-Richard, Simon Bowman, Sue Lester, Per Eriksson, Maija-Leena Eloranta, Johan G Brun, Lasse G Gøransson, Erna Harboe, Joel M Guthridge, Kenneth M Kaufman, Marika Kvarnström, Deborah S Cunninghame Graham, Ketan Patel, Adam J Adler, A Darise Farris, Michael T Brennan, James Chodosh, Rajaram Gopalakrishnan, Michael H Weisman, Swamy Venuturupalli, Daniel J Wallace, Kimberly S Hefner, Glen D Houston, Andrew J W Huang, Pamela J Hughes, David M Lewis, Lida Radfar, Evan S Vista, Contessa E Edgar, Michael D Rohrer, Donald U Stone, Timothy J Vyse, John B Harley, Patrick M Gaffney, Judith A James, Sean Turner, Ilias Alevizos, Juan-Manuel Anaya, Nelson L Rhodus, Barbara M Segal, Courtney G Montgomery, R Hal Scofield, Susan Kovats, Xavier Mariette, Lars Rönnblom, Torsten Witte, Maureen Rischmueller, Marie Wahren-Herlenius, Roald Omdal, Roland Jonsson, Wan-Fai Ng, Gunnel Nordmark, Christopher J Lessard, Kathy L Sivils
Sjögren's syndrome (SS) is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN) pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performed cis-expression quantitative trait locus (eQTL) analyses focusing on differentially expressed type I IFN-inducible transcripts identified through a transcriptome profiling study...
June 22, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28636969/human-virus-derived-small-rnas-can-confer-antiviral-immunity-in-mammals
#2
Yang Qiu, Yanpeng Xu, Yao Zhang, Hui Zhou, Yong-Qiang Deng, Xiao-Feng Li, Meng Miao, Qiang Zhang, Bo Zhong, Yuanyang Hu, Fu-Chun Zhang, Ligang Wu, Cheng-Feng Qin, Xi Zhou
RNA interference (RNAi) functions as a potent antiviral immunity in plants and invertebrates; however, whether RNAi plays antiviral roles in mammals remains unclear. Here, using human enterovirus 71 (HEV71) as a model, we showed HEV71 3A protein as an authentic viral suppressor of RNAi during viral infection. When the 3A-mediated RNAi suppression was impaired, the mutant HEV71 readily triggered the production of abundant HEV71-derived small RNAs with canonical siRNA properties in cells and mice. These virus-derived siRNAs were produced from viral dsRNA replicative intermediates in a Dicer-dependent manner and loaded into AGO, and they were fully active in degrading cognate viral RNAs...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636963/t-bet-runs-interference
#3
Vanja Lazarevic, Susanne Szabo, Laurie H Glimcher
In this issue of Immunity, Iwata et al. (2017) report that the transcription factor T-bet acts as a selective repressor of the type I interferon (IFN) transcriptional program in response to IFN-γ signaling.
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636955/inflammatory-ly6c-high-monocytes-protect-against-candidiasis-through-il-15-driven-nk-cell-neutrophil-activation
#4
Jorge Domínguez-Andrés, Lidia Feo-Lucas, María Minguito de la Escalera, Leticia González, María López-Bravo, Carlos Ardavín
Neutrophils play a crucial role in defense against systemic candidiasis, a disease associated with a high mortality rate in patients receiving immunosuppressive therapy, although the early immune mechanisms that boost the candidacidal activity of neutrophils remain to be defined in depth. Here, we used a murine model of systemic candidiasis to explore the role of inflammatory Ly6C(high) monocytes in NK cell-mediated neutrophil activation during the innate immune response against C. albicans. We found that efficient anti-Candida immunity required a collaborative response between the spleen and kidney, which relied on type I interferon-dependent IL-15 production by spleen inflammatory Ly6C(high) monocytes to drive efficient activation and GM-CSF release by spleen NK cells; this in turn was necessary to boost the Candida killing potential of kidney neutrophils...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636653/the-ebola-virus-vp35-protein-binds-viral-immunostimulatory-and-host-rnas-identified-through-deep-sequencing
#5
Kari A Dilley, Alexander A Voorhies, Priya Luthra, Vinita Puri, Timothy B Stockwell, Hernan Lorenzi, Christopher F Basler, Reed S Shabman
Ebola virus and Marburg virus are members of the Filovirdae family and causative agents of hemorrhagic fever with high fatality rates in humans. Filovirus virulence is partially attributed to the VP35 protein, a well-characterized inhibitor of the RIG-I-like receptor pathway that triggers the antiviral interferon (IFN) response. Prior work demonstrates the ability of VP35 to block potent RIG-I activators, such as Sendai virus (SeV), and this IFN-antagonist activity is directly correlated with its ability to bind RNA...
2017: PloS One
https://www.readbyqxmd.com/read/28634115/delineating-the-roles-of-cellular-and-innate-antiviral-immune-parameters-mediating-ranavirus-susceptibility-using-rainbow-trout-cell-lines
#6
Graeme J Lisser, Nguyen T K Vo, Stephanie J DeWitte-Orr
Frog virus 3 is the type species of the Ranavirus genus and the causative agent of massive mortalities of aquatic species worldwide. A critical step in limiting virus replication, particularly early in infection, is the innate immune response. Presently, little is known regarding what innate immune strategies limit FV3 at the cellular level. To this end, the present study uses two rainbow trout cell lines, RTG-2 and RTgutGC, which demonstrate susceptible and relatively resistant phenotypes to FV3 infection, to elucidate susceptibility factors to FV3...
June 17, 2017: Virus Research
https://www.readbyqxmd.com/read/28631605/loss-of-sendai-virus-c-protein-leads-to-accumulation-of-rig-i-immunostimulatory-defective-interfering-rna
#7
Maria Teresa Sánchez-Aparicio, Dominique Garcin, Charles M Rice, Daniel Kolakofsky, Adolfo García-Sastre, Alina Baum
Retinoic acid inducible gene (RIG-I)-mediated innate immunity plays a pivotal role in defence against virus infections. Previously we have shown that Sendai virus (SeV) defective interfering (DI) RNA functions as an exclusive and potent RIG-I ligand in DI-RNA-rich SeV-Cantell infected cells. To further understand how RIG-I is activated during SeV infection, we used a different interferon (IFN)-inducing SeV strain, recombinant SeVΔC, which, in contrast to SeV-Cantell is believed to stimulate IFN production due to the lack of the SeV IFN antagonist protein C...
June 20, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28630139/functional-interfaces-between-ticam-2-tram-and-ticam-1-trif-in-tlr4-signaling
#8
REVIEW
Kenji Funami, Misako Matsumoto, Hiroyuki Oshiumi, Fuyuhiko Inagaki, Tsukasa Seya
Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS), produces pro-inflammatory cytokines and type I interferons, and associates with a trigger of endotoxin shock. TLR4 is interacted with a TIR domain-containing adaptor molecule-2 (TICAM-2)/TRAM [TRIF (TIR domain-containing adaptor-inducing interferon-β)-related adaptor molecule] via its Toll-interleukin-1 receptor homology (TIR) domain. TICAM-2 acts as a scaffold protein and activates TIR domain-containing adaptor molecule-1 (TICAM-1)/TRIF. According to the structural analysis by NMR, TICAM-2 interacts with TICAM-1 by the acidic amino acids motif, E87/D88/D89...
June 19, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28626076/cardiac-fibroblast-transcriptome-analyses-support-a-role-for-interferogenic-profibrotic-and-inflammatory-genes-in-anti-ssa-ro-associated-congenital-heart-block
#9
Robert M Clancy, Androo J Markham, Tanisha Jackson, Sara E Rasmussen, Miroslav Blumenberg, Jill P Buyon
The signature lesion of SSA/Ro autoantibody-associated congenital heart block (CHB) is fibrosis and a macrophage infiltrate, supporting an experimental focus on cues influencing the fibroblast component. The transcriptomes of human fetal cardiac fibroblasts were analyzed using two complementary approaches. Cardiac injury conditions were simulated in vitro by incubating human fetal cardiac fibroblasts with supernatants from macrophages transfected with the SSA/Ro-associated hY3. The top ten upregulated transcripts in the stimulated fibroblasts reflected a type I interferon (IFN) response (e...
June 16, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28625521/protective-efficacy-of-multivalent-replication-abortive-vaccine-strains-in-horses-against-african-horse-sickness-virus-challenge
#10
Valeria Lulla, Andres Losada, Sylvie Lecollinet, Adeline Kerviel, Thomas Lilin, Corinne Sailleau, Cecile Beck, Stephan Zientara, Polly Roy
African horse sickness virus (AHSV) is an orbivirus, a member of the Reoviridae family. Nine different serotypes have been described so far. AHSV is vectored by Culicoides spp. to equids, causing high mortality, particularly in horses, with considerable economic impacts. For development of a safe attenuated vaccine, we previously established an efficient reverse genetics (RG) system to generate Entry Competent Replication-Abortive (ECRA) virus strains, for all nine serotypes and demonstrated the vaccine potential of these strains in type I interferon receptor (IFNAR)-knockout mice...
June 15, 2017: Vaccine
https://www.readbyqxmd.com/read/28623741/oxidized-ldl-activated-eosinophil-polarize-macrophage-phenotype-from-m2-to-m1-through-activation-of-cd36-scavenger-receptor
#11
Minghui Qin, Lai Wang, Fuqiang Li, Mingjie Yang, Lei Song, Fang Tian, Ada Yukht, Prediman K Shah, Marc E Rothenberg, Behrooz G Sharifi
BACKGROUND AND AIMS: Inflammation, particularly innate immunity, plays an important role in cardiovascular diseases. The aim of this study was to investigate whether atherogenic determinants such as oxidized LDL modulate the phenotype of eosinophils. METHODS: Cultured eosinophils were treated with oxidized LDL and the expression of selective inflammatory and anti-inflammatory cytokines was determined. In addition, the eosinophil receptor and signaling that mediate these events were identified...
May 20, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28623559/ifn-%C3%AE-induced-reactive-oxygen-species-and-mitochondrial-damage-contribute-to-muscle-impairment-and-inflammation-maintenance-in-dermatomyositis
#12
Alain Meyer, Gilles Laverny, Yves Allenbach, Elise Grelet, Vanessa Ueberschlag, Andoni Echaniz-Laguna, Béatrice Lannes, Ghada Alsaleh, Anne Laure Charles, François Singh, Joffrey Zoll, Evelyne Lonsdorfer, François Maurier, Olivier Boyer, Jacques-Eric Gottenberg, Anne Sophie Nicot, Jocelyn Laporte, Olivier Benveniste, Daniel Metzger, Jean Sibilia, Bernard Geny
Dermatomyositis (DM) is an autoimmune disease associated with enhanced type I interferon (IFN) signalling in skeletal muscle, but the mechanisms underlying muscle dysfunction and inflammation perpetuation remain unknown. Transcriptomic analysis of early untreated DM muscles revealed that the main cluster of down-regulated genes was mitochondria-related. Histochemical, electron microscopy, and in situ oxygraphy analysis showed mitochondrial abnormalities, including increased reactive oxygen species (ROS) production and decreased respiration, which was correlated with low exercise capacities and a type I IFN signature...
June 16, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28623344/an-essential-role-of-pi3k-in-the-control-of-west-nile-virus-infection
#13
Leilei Wang, Long Yang, Erol Fikrig, Penghua Wang
The phosphatidyl-inositol-3 kinases (PI3K) pathway regulates a variety of cellular processes, including cell proliferation, RNA processing, protein translation, autophagy, apoptosis and antiviral immunity. Many viruses depend on PI3K signaling for replication. However, its role in flaviviral infection has not been clearly defined. Here we report that PI3K signaling is critical for the control of West Nile virus (WNV) infection by regulating type I IFN (IFN-I) response. Inhibition of PI3K activity by 3-methyl adenine (3-MA), Wortmannin (WM) and LY294002 (LY) increased viral titers by 3-16 folds in primary mouse macrophages, embryonic fibroblasts and human cell lines...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623086/the-transcription-factor-t-bet-limits-amplification-of-type-i-ifn-transcriptome-and-circuitry-in-t-helper-1-cells
#14
Shigeru Iwata, Yohei Mikami, Hong-Wei Sun, Stephen R Brooks, Dragana Jankovic, Kiyoshi Hirahara, Atsushi Onodera, Han-Yu Shih, Takeshi Kawabe, Kan Jiang, Toshinori Nakayama, Alan Sher, John J O'Shea, Fred P Davis, Yuka Kanno
Host defense requires the specification of CD4(+) helper T (Th) cells into distinct fates, including Th1 cells that preferentially produce interferon-γ (IFN-γ). IFN-γ, a member of a large family of anti-pathogenic and anti-tumor IFNs, induces T-bet, a lineage-defining transcription factor for Th1 cells, which in turn supports IFN-γ production in a feed-forward manner. Herein, we show that a cell-intrinsic role of T-bet influences how T cells perceive their secreted product in the environment. In the absence of T-bet, IFN-γ aberrantly induced a type I IFN transcriptomic program...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28619150/alpha-beta-interferon-receptor-deficiency-in-mice-significantly-enhances-susceptibility-of-the-animals-to-pseudorabies-virus-infection
#15
Jingyun Wei, Yanmei Ma, Long Wang, Xiaojuan Chi, Ruoxiang Yan, Song Wang, Xinxin Li, Xiaoyong Chen, Wenhan Shao, Ji-Long Chen
Pseudorabies virus, one of the neurotropic viruses, can infect numerous mammals. In particular, pseudorabies virus infection of swine occurs worldwide, and is a major threat to swine industry. However, the mechanism underlying the interaction between pseudorabies virus and host innate immune system is not fully understood. Here, we investigated the involvement of interferon α/β (IFN-α/β) receptor (IFNAR) in the pathogenesis of pseudorabies virus in a mouse model. The results showed that IFNAR-deficient (IFNAR(-/-)) mice were highly susceptible to the virus infection, as evidenced by markedly reduced survival rate of infected animals and increased viral replication...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28619037/ifn-%C3%AE-1-with-th17-axis-cytokines-and-ifn-%C3%AE-define-different-subsets-in-systemic-lupus-erythematosus-sle
#16
Vilija Oke, Susanna Brauner, Anders Larsson, Johanna Gustafsson, Agneta Zickert, Iva Gunnarsson, Elisabet Svenungsson
BACKGROUND: Interferon (IFN)-α is thought to have a pivotal role in systemic lupus erythematosus (SLE), and type III IFNs (IFN-λ) were recently also associated with SLE. In this study, we measured levels of IFN-α, IFN-λ1, and related cytokines, such as IL-17A, IL-23, and interferon-γ-induced protein 10 (IP-10), in a Karolinska University Hospital cohort of patients with SLE and control subjects. The objective of the study was to investigate if cytokine measurements could identify different subsets of patients with active SLE and higher disease damage...
June 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28615418/cutting-edge-activation-of-sting-in-t-cells-induces-type-i-ifn-responses-and-cell-death
#17
Bridget Larkin, Vladimir Ilyukha, Maxim Sorokin, Anton Buzdin, Edouard Vannier, Alexander Poltorak
Stimulator of interferon genes (STING) was initially described as a sensor of intracellular bacterial and viral DNA and a promising adjuvant target in innate immune cells; more recently STING has also been shown to detect endogenous DNA and play a role in tumor immunity and autoimmune disease development. Thus far STING has been studied in macrophages and dendritic cells. In this study, to our knowledge we provide the first evidence of STING activation in T cells, in which STING agonists not only provoke type I IFN production and IFN-stimulated gene expression, mirroring the response of innate cells, but are also capable of activating cell stress and death pathways...
June 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28614789/type-i-interferons-suppress-viral-replication-but-contribute-to-t-cell-depletion-and-dysfunction-during-chronic-hiv-1-infection
#18
Liang Cheng, Haisheng Yu, Guangming Li, Feng Li, Jianping Ma, Jingyun Li, Liqun Chi, Liguo Zhang, Lishan Su
The direct link between sustained type I interferon (IFN-I) signaling and HIV-1-induced immunopathogenesis during chronic infection remains unclear. Here we report studies using a monoclonal antibody to block IFN-α/β receptor 1 (IFNAR1) signaling during persistent HIV-1 infection in humanized mice (hu-mice). We discovered that, during chronic HIV-1 infection, IFNAR blockade increased viral replication, which was correlated with elevated T cell activation. Thus, IFN-Is suppress HIV-1 replication during the chronic phase but are not essential for HIV-1-induced aberrant immune activation...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28614719/systemic-virus-infections-differentially-modulate-cell-cycle-state-and-functionality-of-long-term-hematopoietic-stem-cells-in%C3%A2-vivo
#19
Christoph Hirche, Theresa Frenz, Simon F Haas, Marius Döring, Katharina Borst, Pia-K Tegtmeyer, Ilija Brizic, Stefan Jordan, Kirsten Keyser, Chintan Chhatbar, Eline Pronk, Shuiping Lin, Martin Messerle, Stipan Jonjic, Christine S Falk, Andreas Trumpp, Marieke A G Essers, Ulrich Kalinke
Quiescent long-term hematopoietic stem cells (LT-HSCs) are efficiently activated by type I interferon (IFN-I). However, this effect remains poorly investigated in the context of IFN-I-inducing virus infections. Here we report that both vesicular stomatitis virus (VSV) and murine cytomegalovirus (MCMV) infection induce LT-HSC activation that substantially differs from the effects triggered upon injection of synthetic IFN-I-inducing agents. In both infections, inflammatory responses had to exceed local thresholds within the bone marrow to confer LT-HSC cell cycle entry, and IFN-I receptor triggering was not critical for this activation...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28614389/immunological-dynamics-associated-with-rapid-virological-response-during-the-early-phase-of-type-i-interferon-therapy-in-patients-with-chronic-hepatitis-c
#20
Jae-Won Lee, Won Kim, Eun-Kyung Kwon, Yuri Kim, Hyun Mu Shin, Dong-Hyun Kim, Chan-Ki Min, Ji-Yeob Choi, Won-Woo Lee, Myung-Sik Choi, Byeong Gwan Kim, Nam-Hyuk Cho
Type I interferons (IFNs) play an important role in antiviral immunity as well as immunopathogenesis of diverse chronic viral infections. However, the precise mechanisms regulating the multifaceted effects of type I IFNs on the immune system and pathological inflammation still remain unclear. In order to assess the immunological dynamics associated with rapid viral clearance in chronic hepatitis C patients during the acute phase of type I IFN therapy, we analyzed multiple parameters of virological and immunological responses in a cohort of 59 Korean hepatitis C patients who received pegylated IFN-α and ribavirin (IFN/RBV)...
2017: PloS One
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