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Stimulator of interferon genes

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https://www.readbyqxmd.com/read/27929099/stat1-is-essential-for-the-inhibition-of-hepatitis-c-virus-replication-by-interferon-%C3%AE-but-not-by-interferon-%C3%AE
#1
Shota Yamauchi, Kenji Takeuchi, Kazuyasu Chihara, Chisato Honjoh, Yuji Kato, Hatsumi Yoshiki, Hak Hotta, Kiyonao Sada
Interferon-α (IFN-α) and IFN-λ are structurally distinct cytokines that bind to different receptors, but induce expression of similar sets of genes through Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathways. The difference between IFN-α and IFN-λ signaling remains poorly understood. Here, using the CRISPR/Cas9 system, we examine the role of STAT1 and STAT2 in the inhibition of hepatitis C virus (HCV) replication by IFN-α and IFN-λ. Treatment with IFN-α increases expression of IFN-stimulated genes (ISGs) such as double-stranded RNA-activated protein kinase (PKR) and decreases viral RNA and protein levels in HCV-infected Huh-7...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27923923/antiviral-innate-immune-response-interferes-with-the-formation-of-replication-associated-membrane-structures-induced-by-a-positive-strand-rna-virus
#2
Diede Oudshoorn, Barbara van der Hoeven, Ronald W A L Limpens, Corrine Beugeling, Eric J Snijder, Montserrat Bárcena, Marjolein Kikkert
: Infection with nidoviruses like corona- and arteriviruses induces a reticulovesicular network of interconnected endoplasmic reticulum (ER)-derived double-membrane vesicles (DMVs) and other membrane structures. This network is thought to accommodate the viral replication machinery and protect it from innate immune detection. We hypothesized that the innate immune response has tools to counteract the formation of these virus-induced replication organelles in order to inhibit virus replication...
December 6, 2016: MBio
https://www.readbyqxmd.com/read/27916855/comparative-proteome-analysis-of-porcine-jejunum-tissues-in-response-to-a-virulent-strain-of-porcine-epidemic-diarrhea-virus-and-its-attenuated-strain
#3
Zhonghua Li, Fangzhou Chen, Shiyi Ye, Xiaozhen Guo, Atta Muhanmmad Memon, Meizhou Wu, Qigai He
Porcine epidemic diarrhea virus (PEDV), a predominant cause of acute enteric infection, leads to severe dehydrating diarrhea and mortality in piglets all over the world. A virulent PEDV YN13 strain, isolated in our laboratory, was attenuated to yield an attenuated PEDV strain YN144. To better understand the pathogenesis mechanism and the virus-host interaction during infection with both PEDV YN13 and YN144 strains, a comparative proteomic analysis was carried out to investigate the proteomic changes produced in the primary target organ, using isobaric tags for relative and absolute quantitation (iTRAQ) labeling, followed by liquid chromatography tandem-mass spectrometry (LC-MS/MS)...
November 29, 2016: Viruses
https://www.readbyqxmd.com/read/27914808/influenza-a-virus-ns1-protein-induced-a20-contributes-to-viral-replication-by-suppressing-interferon-induced-antiviral-response
#4
Wenjing Feng, Xiaoning Sun, Ning Shi, Maolin Zhang, Zhenhong Guan, Ming Duan
The innate immune response provides the first line of defense against viruses and other pathogens by responding to specific microbial molecules. A20 is a cytoplasmic ubiquitin-editing protein that negatively regulates the retinoic acid-inducible gene I (RIG-I)-mediated activation of interferon regulatory factors (IRF) 3. Here, we found that influenza A virus (IAV) non-structural protein (NS) 1 dramatically induced the protein level of A20 in A549 cells whose expression levels were positively associated with the viral virulence...
December 1, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27914741/maternal-bcg-scar-is-associated-with-increased-infant-proinflammatory-immune-responses
#5
Patrice Akusa Mawa, Emily L Webb, Abdelali Filali-Mouhim, Gyaviira Nkurunungi, Rafick-Pierre Sekaly, Swaib Abubaker Lule, Sarah Prentice, Stephen Nash, Hazel M Dockrell, Alison M Elliott, Stephen Cose
INTRODUCTION: Prenatal exposures such as infections and immunisation may influence infant responses. We had an opportunity to undertake an analysis of innate responses in infants within the context of a study investigating the effects of maternal mycobacterial exposures and infection on BCG vaccine-induced responses in Ugandan infants. MATERIAL AND METHODS: Maternal and cord blood samples from 29 mother-infant pairs were stimulated with innate stimuli for 24h and cytokines and chemokines in supernatants were measured using the Luminex® assay...
November 30, 2016: Vaccine
https://www.readbyqxmd.com/read/27912061/tumor-interferon-signaling-regulates-a-multigenic-resistance-program-to-immune-checkpoint-blockade
#6
Joseph L Benci, Bihui Xu, Yu Qiu, Tony J Wu, Hannah Dada, Christina Twyman-Saint Victor, Lisa Cucolo, David S M Lee, Kristen E Pauken, Alexander C Huang, Tara C Gangadhar, Ravi K Amaravadi, Lynn M Schuchter, Michael D Feldman, Hemant Ishwaran, Robert H Vonderheide, Amit Maity, E John Wherry, Andy J Minn
Therapeutic blocking of the PD1 pathway results in significant tumor responses, but resistance is common. We demonstrate that prolonged interferon signaling orchestrates PDL1-dependent and PDL1-independent resistance to immune checkpoint blockade (ICB) and to combinations such as radiation plus anti-CTLA4. Persistent type II interferon signaling allows tumors to acquire STAT1-related epigenomic changes and augments expression of interferon-stimulated genes and ligands for multiple T cell inhibitory receptors...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27909056/interferons-induce-expression-of-samhd1-in-monocytes-through-downregulation-of-mir-181a-and-mir-30a
#7
Maximilan Riess, Nina V Fuchs, Adam Idica, Matthias Hamdorf, Egbert Flory, Irene Munk Pedersen, Renate König
SAMHD1 is a phosphohydrolase maintaining cellular dNTP homeostasis but also acts as a critical regulator in innate immune responses due to its antiviral activity and association with autoimmune disease leading to aberrant activation of interferon. SAMHD1 expression is differentially regulated by interferon in certain primary cells, but the underlying mechanism is not understood. Here, we report a detailed characterization of the promotor region, the 5' and 3' untranslated region (UTR) of SAMHD1, and the mechanism responsible for the cell-type dependent upregulation of SAMHD1 protein by interferon...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27907166/vaccinia-virus-protein-c6-inhibits-type-i-ifn-signalling-in-the-nucleus-and-binds-to-the-transactivation-domain-of-stat2
#8
Jennifer H Stuart, Rebecca P Sumner, Yongxu Lu, Joseph S Snowden, Geoffrey L Smith
The type I interferon (IFN) response is a crucial innate immune signalling pathway required for defense against viral infection. Accordingly, the great majority of mammalian viruses possess means to inhibit this important host immune response. Here we show that vaccinia virus (VACV) strain Western Reserve protein C6, is a dual function protein that inhibits the cellular response to type I IFNs in addition to its published function as an inhibitor of IRF-3 activation, thereby restricting type I IFN production from infected cells...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27907031/in-vitro-pre-clinical-validation-of-suicide-gene-modified-anti-cd33-redirected-chimeric-antigen-receptor-t-cells-for-acute-myeloid-leukemia
#9
Kentaro Minagawa, Muhammad O Jamil, Mustafa Al-Obaidi, Larisa Pereboeva, Donna Salzman, Harry P Erba, Lawrence S Lamb, Ravi Bhatia, Shin Mineishi, Antonio Di Stasi
BACKGROUND: Approximately fifty percent of patients with acute myeloid leukemia can be cured with current therapeutic strategies which include, standard dose chemotherapy for patients at standard risk of relapse as assessed by cytogenetic and molecular analysis, or high-dose chemotherapy with allogeneic hematopoietic stem cell transplant for high-risk patients. Despite allogeneic hematopoietic stem cell transplant about 25% of patients still succumb to disease relapse, therefore, novel strategies are needed to improve the outcome of patients with acute myeloid leukemia...
2016: PloS One
https://www.readbyqxmd.com/read/27905537/unique-nonstructural-proteins-of-pneumonia-virus-of-mice-pvm-promote-degradation-of-interferon-ifn-pathway-components-and-ifn-stimulated-gene-proteins
#10
Jayeeta Dhar, Sailen Barik
Pneumonia Virus of Mice (PVM) is the only virus that shares the Pneumovirus genus of the Paramyxoviridae family with Respiratory Syncytial Virus (RSV). A deadly mouse pathogen, PVM has the potential to serve as a robust animal model of RSV infection, since human RSV does not fully replicate the human pathology in mice. Like RSV, PVM also encodes two nonstructural proteins that have been implicated to suppress the IFN pathway, but surprisingly, they exhibit no sequence similarity with their RSV equivalents. The molecular mechanism of PVM NS function, therefore, remains unknown...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27903862/improved-cancer-immunotherapy-by-a-cd25-mimobody-conferring-selectivity-to-human-interleukin-2
#11
Natalia Arenas-Ramirez, Chao Zou, Simone Popp, Daniel Zingg, Barbara Brannetti, Emmanuelle Wirth, Thomas Calzascia, Jiri Kovarik, Lukas Sommer, Gerhard Zenke, Janine Woytschak, Catherine H Regnier, Andreas Katopodis, Onur Boyman
Interleukin-2 (IL-2) immunotherapy is an attractive approach in treating advanced cancer. However, by binding to its IL-2 receptor α (CD25) subunit, IL-2 exerts unwanted effects, including stimulation of immunosuppressive regulatory T cells (Tregs) and contribution to vascular leak syndrome. We used a rational approach to develop a monoclonal antibody to human IL-2, termed NARA1, which acts as a high-affinity CD25 mimic, thereby minimizing association of IL-2 with CD25. The structure of the IL-2-NARA1 complex revealed that NARA1 occupies the CD25 epitope of IL-2 and precisely overlaps with CD25...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27903802/a-protective-role-for-il-1-signaling-during-mouse-adenovirus-type-1-induced-encephalitis
#12
Luiza A Castro-Jorge, Carla Pretto, Asa Smith, Oded Foreman, Kelly E Carnahan, Katherine R Spindler
: IL-1β, an inflammatory cytokine and IL-1 receptor ligand, has diverse activities in the brain. We examined whether IL-1 signaling contributes to the encephalitis observed in mouse adenovirus type 1 (MAV-1) infection, using mice lacking the IL-1 receptor, Il1r1(-/-) Il1r1(-/-) mice had lower survival, higher disruption of the blood-brain barrier (BBB), higher brain viral loads, and higher brain inflammatory cytokines and chemokines than control C57BL/6 mice. We also examined infections of mice defective in IL-1β production (Pycard(-/-)mice) and mice defective in trafficking of TLRs to the endosome (Unc93b1(-/-) mice)...
November 30, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27899525/reactive-oxygen-species-induce-virus-independent-mavs-oligomerization-in-systemic-lupus-erythematosus
#13
Iwona A Buskiewicz, Theresa Montgomery, Elizabeth C Yasewicz, Sally A Huber, Michael P Murphy, Richard C Hartley, Ryan Kelly, Mary K Crow, Andras Perl, Ralph C Budd, Andreas Koenig
The increased expression of genes induced by type I interferon (IFN) is characteristic of viral infections and systemic lupus erythematosus (SLE). We showed that mitochondrial antiviral signaling (MAVS) protein, which normally forms a complex with retinoic acid gene I (RIG-I)-like helicases during viral infection, was activated by oxidative stress independently of RIG-I helicases. We found that chemically generated oxidative stress stimulated the formation of MAVS oligomers, which led to mitochondrial hyperpolarization and decreased adenosine triphosphate production and spare respiratory capacity, responses that were not observed in similarly treated cells lacking MAVS...
November 29, 2016: Science Signaling
https://www.readbyqxmd.com/read/27899441/interferon-regulatory-factor-2-protects-mice-from-lethal-viral-neuroinvasion
#14
Melody M H Li, Leonia Bozzacco, Hans-Heinrich Hoffmann, Gaëlle Breton, Jakob Loschko, Jing W Xiao, Sébastien Monette, Charles M Rice, Margaret R MacDonald
The host responds to virus infection by activating type I interferon (IFN) signaling leading to expression of IFN-stimulated genes (ISGs). Dysregulation of the IFN response results in inflammatory diseases and chronic infections. In this study, we demonstrate that IFN regulatory factor 2 (IRF2), an ISG and a negative regulator of IFN signaling, influences alphavirus neuroinvasion and pathogenesis. A Sindbis virus strain that in wild-type (WT) mice only causes disease when injected into the brain leads to lethal encephalitis in Irf2(-/-) mice after peripheral inoculation...
November 29, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27898968/post-artificial-insemination-supplementation-with-calcium-salts-of-soybean-oil-influences-pregnancy-establishment-factors-in-beef-cows
#15
R S Cipriano, R F Cooke, A D Rodrigues, L G T Silva, D W Bohnert, R S Marques, J L M Vasconcelos, A V Pires, R L A Cerri
The objective of this experiment was to compare hormonal, uterine, and conceptus factors associated with pregnancy establishment in beef cows supplemented or not with Ca salts of soybean oil (CSSO) for 21 d beginning after timed AI. One hundred lactating multiparous Nelore cows were allocated to 20 groups of 5 cows/group and timed inseminated on d 0 of the experiment. After AI, groups were randomly assigned to receive (as-fed basis) 100 g of protein-mineral mix + 100 g of ground corn per cow per day, in addition to 1) 100 g/cow daily of CSSO ( = 10) or 2) 100 g/cow daily of kaolin (CON; rumen-inert indigestible substance; = 10)...
November 2016: Journal of Animal Science
https://www.readbyqxmd.com/read/27897452/characterization-of-two-recombinant-hvt-ibd-vaccines-by-vp2-insert-detection-and-cell-mediated-immunity-after-vaccination-of-specific-pathogen-free-chickens
#16
Fiona Ingrao, Fabienne Rauw, Thierry van den Berg, Bénédicte Lambrecht
Infectious bursal disease (IBD) is an avian viral disease that causes severe economic losses in the poultry industry worldwide. The live IBD virus (IBDV) has a potential immunosuppressive effect. Currently available IBDV vaccines have shortcomings, prompting the development of safer and more effective vaccination approaches, including the use of the recombinant turkey herpesvirus vaccine expressing the immunogenic structural VP2 protein of IBDV (rHVT-IBD). The objectives of this study were twofold: (i) to develop in vitro assays and molecular tools to detect the VP2 protein and gene, and (ii) to evaluate cell-mediated immunity (CMI) induced by rHVT-IBD vaccination of day-old specific pathogen-free chickens...
November 29, 2016: Avian Pathology: Journal of the W.V.P.A
https://www.readbyqxmd.com/read/27896670/the-activation-of-the-ifn%C3%AE-induction-signaling-pathway-in-porcine-alveolar-macrophages-by-porcine-reproductive-and-respiratory-syndrome-virus-is-variable
#17
Christopher C Overend, Junru Cui, Marvin J Grubman, Antonio E Garmendia
BACKGROUND: It has been recognized that the expression of type I interferon (IFNα/β) may be suppressed during infection with porcine reproductive, respiratory syndrome virus (PRRSV). This causes profound negative effects on both the innate and adaptive immunity of the host resulting in persistence of infection. OBJECTIVE: Test the effects of PRRSV infection of porcine alveolar macrophages (PAMs), the main target cell, on the expression of interferon beta (IFNβ) and downstream signaling events...
November 28, 2016: Veterinary Research Communications
https://www.readbyqxmd.com/read/27893714/the-lim-protein-ajuba-promotes-colorectal-cancer-cell-survival-through-suppression-of-jak1-stat1-ifit2-network
#18
H Jia, L Song, Q Cong, J Wang, H Xu, Y Chu, Q Li, Y Zhang, X Zou, C Zhang, Y E Chin, X Zhang, Z Li, K Zhu, B Wang, H Peng, Z Hou
The LIM protein AJUBA is a scaffold protein participating in the regulation of cell adhesion, mitosis, DNA damage, cell differentiation, proliferation, migration and gene transcription. However, its roles in tumorigenesis and progression are poorly defined. Here, we report that AJUBA is highly expressed in colorectal cancer (CRC) and promotes CRC cell growth in culture and in xenografted mice via an inhibition of apoptosis. AJUBA represses the expression of IFIT2 gene, an interferon-stimulated gene and a known apoptosis inducer and tumour suppressor to mediate its resistance to apoptosis...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27889408/an-rna-based-fluorescent-biosensor-for-high-throughput-analysis-of-the-cgas-cgamp-sting-pathway
#19
Debojit Bose, Yichi Su, Assaf Marcus, David H Raulet, Ming C Hammond
In mammalian cells, the second messenger (2'-5',3'-5') cyclic guanosine monophosphate-adenosine monophosphate (2',3'-cGAMP), is produced by the cytosolic DNA sensor cGAMP synthase (cGAS), and subsequently bound by the stimulator of interferon genes (STING) to trigger interferon response. Thus, the cGAS-cGAMP-STING pathway plays a critical role in pathogen detection, as well as pathophysiological conditions including cancer and autoimmune disorders. However, studying and targeting this immune signaling pathway has been challenging due to the absence of tools for high-throughput analysis...
November 18, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/27887993/isg15-in-sickness-and-in-health
#20
REVIEW
Mark Hermann, Dusan Bogunovic
ISG15 is a type I interferon (IFN)-inducible gene encoding a protein with pleiotropic functions, acting both as a soluble molecule and as a protein modifier. Surprisingly, and despite the antiviral functions of ISG15 described in mice, humans born with inactivating mutations of ISG15 do not present with any overt viral phenotype, but are highly susceptible to environmental mycobacteria and have autoinflammatory disease presentations. In vitro, ISG15 deficiency also leads to persistently high levels of type I IFN-stimulated gene expression and to increased resistance to all viruses tested to date...
November 22, 2016: Trends in Immunology
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