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Stimulator of interferon genes

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https://www.readbyqxmd.com/read/28548080/discovery-of-first-in-class-reversible-dual-small-molecule-inhibitors-against-g9a-and-dnmts-in-hematological-malignancies
#1
Edurne San José-Enériz, Xabier Agirre, Obdulia Rabal, Amaia Vilas-Zornoza, Juan A Sanchez-Arias, Estibaliz Miranda, Ana Ugarte, Sergio Roa, Bruno Paiva, Ander Estella-Hermoso de Mendoza, Rosa María Alvarez, Noelia Casares, Victor Segura, José I Martín-Subero, François-Xavier Ogi, Pierre Soule, Clara M Santiveri, Ramón Campos-Olivas, Giancarlo Castellano, Maite Garcia Fernandez de Barrena, Juan Roberto Rodriguez-Madoz, Maria José García-Barchino, Juan Jose Lasarte, Matias A Avila, Jose Angel Martinez-Climent, Julen Oyarzabal, Felipe Prosper
The indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favoured development of epigenetic drugs. In this study, we design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity. In vitro treatment of haematological neoplasia (acute myeloid leukaemia-AML, acute lymphoblastic leukaemia-ALL and diffuse large B-cell lymphoma-DLBCL) with the lead compound CM-272, inhibits cell proliferation and promotes apoptosis, inducing interferon-stimulated genes and immunogenic cell death...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28546020/the-evolution-and-functional-characterization-of-miiuy-croaker-interferon-regulatory-factor-9-involved-in-immune-response
#2
Qiong Yang, Junxia Cui, Weihua Song, Xueyan Zhao, Tianjun Xu
Interferon regulatory factors (IRFs) are transcription factors playing important roles in regulating the expression of type I interferons (IFNs) and IFN-stimulated genes. IRF9 is one of the IRF family gene members which belongs to the IRF4 subfamily. Mammalian IRF9 has been known to be involved in antiviral response as the DNA sequence recognition subunit of IFN-stimulated gene factor 3 (ISGF3) complex. In fish, only a few studies investigated the characteristics of IRF9 and the role in IFN signaling. In this study, we identify the IRF9 gene from miiuy croaker (mmiIRF9) and studied its feature and function...
May 22, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28545670/inhibitory-mechanism-of-five-natural-flavonoids-against-murine-norovirus
#3
Dong Joo Seo, Changsun Choi
BACKGROUND: Human noroviruses (HuNoV), which are responsible for acute gastroenteritis, are becoming a serious public health concern worldwide. Since no effective antiviral drug or vaccine for HuNoV has been developed yet, some natural extracts and their active components have been investigated for their ability to inhibit noroviruses. However, their exact antiviral mechanisms have not been investigated. PURPOSE: This study was performed to investigate the expression of interferon (IFN)-α, IFN-λ, tumor necrosis factor-α (TNF-α), Mx, and zinc finger CCCH type antiviral protein 1 (ZAP), 2'-5' oligo (A) synthetase (OAS), and inducible nitric oxide synthase (iNOS) in RAW 264...
July 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28543875/unconjugated-interferon-stimulated-gene-15-specifically-interacts-with-the-hepatitis-c-virus-ns5a-protein-via-domain-i
#4
Nanae Minami, Takayuki Abe, Lin Deng, Chieko Matsui, Takasuke Fukuhara, Yoshiharu Matsuura, Ikuo Shoji
Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein induced by type I interferon. Although several groups have reported ISGylation of the HCV NS5A protein, it is still unclear whether ISGylation of NS5A has anti-viral or pro-viral effects in HCV infection. In the present study, we examined the role of ISGylation-independent, unconjugated ISG15 in HCV infection. Immunoprecipitation analyses revealed that ISG15 specifically interacted with NS5A domain I. The ISG15 mutants lacking a C-terminal glycine residue essential for ISGylation still interacted with NS5A protein...
May 25, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28542711/preventing-relapse-after-haematopoietic-stem-cell-transplantation-for-acute-leukaemia-the-role-of-post-transplantation-minimal-residual-disease-mrd-monitoring-and-mrd-directed-intervention
#5
REVIEW
Xiao-Dong Mo, Meng Lv, Xiao-Jun Huang
Relapse is the main cause of treatment failure after allogeneic haematopoietic stem cell transplantation (allo-HSCT) for acute leukaemia (AL). Post-transplantation minimal residual disease (MRD) monitoring enables risk stratification and identifies AL patients at higher risk of relapse. MRD assessment primarily involves the determination of leukaemia-associated immunophenotypic patterns using multiparameter flow cytometry, and the polymerase chain reaction (PCR)-based evaluation of expression levels of leukaemia-related genes (specific reciprocal gene rearrangements and other mutation types)...
May 23, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28542609/potent-and-selective-inhibition-of-pathogenic-viruses-by-engineered-ubiquitin-variants
#6
Wei Zhang, Ben A Bailey-Elkin, Robert C M Knaap, Baldeep Khare, Tim J Dalebout, Garrett G Johnson, Puck B van Kasteren, Nigel J McLeish, Jun Gu, Wenguang He, Marjolein Kikkert, Brian L Mark, Sachdev S Sidhu
The recent Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola and Zika virus outbreaks exemplify the continued threat of (re-)emerging viruses to human health, and our inability to rapidly develop effective therapeutic countermeasures. Many viruses, including MERS-CoV and the Crimean-Congo hemorrhagic fever virus (CCHFV) encode deubiquitinating (DUB) enzymes that are critical for viral replication and pathogenicity. They bind and remove ubiquitin (Ub) and interferon stimulated gene 15 (ISG15) from cellular proteins to suppress host antiviral innate immune responses...
May 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542326/the-murine-cytomegalovirus-m35-protein-antagonizes-type-i-ifn-induction-downstream-of-pattern-recognition-receptors-by-targeting-nf-%C3%AE%C2%BAb-mediated-transcription
#7
Baca Chan, Vladimir Gonçalves Magalhães, Niels A W Lemmermann, Vanda Juranić Lisnić, Markus Stempel, Kendra A Bussey, Elisa Reimer, Jürgen Podlech, Stefan Lienenklaus, Matthias J Reddehase, Stipan Jonjić, Melanie M Brinkmann
The type I interferon (IFN) response is imperative for the establishment of the early antiviral immune response. Here we report the identification of the first type I IFN antagonist encoded by murine cytomegalovirus (MCMV) that shuts down signaling following pattern recognition receptor (PRR) sensing. Screening of an MCMV open reading frame (ORF) library identified M35 as a novel and strong negative modulator of IFNβ promoter induction following activation of both RNA and DNA cytoplasmic PRR. Additionally, M35 inhibits the proinflammatory cytokine response downstream of Toll-like receptors (TLR)...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28536351/oncolytic-vesicular-stomatitis-virus-as-a-viro-immunotherapy-defeating-cancer-with-a-hammer-and-anvil
#8
REVIEW
Michael Karl Melzer, Arturo Lopez-Martinez, Jennifer Altomonte
Oncolytic viruses have gained much attention in recent years, due, not only to their ability to selectively replicate in and lyse tumor cells, but to their potential to stimulate antitumor immune responses directed against the tumor. Vesicular stomatitis virus (VSV), a negative-strand RNA virus, is under intense development as an oncolytic virus due to a variety of favorable properties, including its rapid replication kinetics, inherent tumor specificity, and its potential to elicit a broad range of immunomodulatory responses to break immune tolerance in the tumor microenvironment...
February 10, 2017: Biomedicines
https://www.readbyqxmd.com/read/28535250/evidence-for-the-deregulation-of-protein-turnover-pathways-in-atm-deficient-mouse-cerebellum-an-organotypic-study
#9
Catherine D Kim, Ryan E Reed, Meredith A Juncker, Zhide Fang, Shyamal D Desai
Interferon-stimulated gene 15 (ISG15), an antagonist of the ubiquitin pathway, is elevated in cells and brain tissues obtained from ataxia telangiectasia (A-T) patients. Previous studies reveal that an elevated ISG15 pathway inhibits ubiquitin-dependent protein degradation, leading to activation of basal autophagy as a compensatory mechanism for protein turnover in A-T cells. Also, genotoxic stress (ultraviolet [UV] radiation) deregulates autophagy and induces aberrant degradation of ubiquitylated proteins in A-T cells...
May 23, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28533548/lack-of-inflammatory-gene-expression-in-bats-a-unique-role-for-a-transcription-repressor
#10
Arinjay Banerjee, Noreen Rapin, Trent Bollinger, Vikram Misra
In recent years viruses similar to those that appear to cause no overt disease in bats have spilled-over to humans and other species causing serious disease. Since pathology in such diseases is often attributed to an over-active inflammatory response, we tested the hypothesis that bat cells respond to stimulation of their receptors for viral ligands with a strong antiviral response, but unlike in human cells, the inflammatory response is not overtly activated. We compared the response of human and bat cells to poly(I:C), a viral double-stranded RNA surrogate...
May 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28532825/growth-performance-reproductive-traits-and-offspring-survivability-of-genetically-modified-rams-overexpressing-toll-like-receptor-4
#11
Yu-Chang Yao, Hong-Bing Han, Xu-Ting Song, Shou-Long Deng, Yu-Feng Liu, Ming-Hai Lu, Yun-Hai Zhang, Mei-Yu Qi, Hai-Juan He, Su-Mei Wang, Guo-Shi Liu, Wu Li, Zheng-Xing Lian
Genetic modification provides a means to enhancing disease resistance in animals. Toll-like receptor 4 (TLR4), a member of the TLR family, is critical for the recognition of lipopolysaccharide (LPS)/endotoxin from Gram-negative bacteria by host immune cells, which initiates cell activation and subsequently triggers a proinflammatory response to the invading pathogens. In this study, the first generation of genetically modified (GM) sheep overexpressing TLR4 was produced by microinjection for better disease resistance...
July 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28528205/heterotrimeric-complex-of-p38-mapk-pkc%C3%AE-and-tirap-is-required-for-ap1-mediated-inflammatory-response
#12
Mirza S Baig, Dongfang Liu, Kannan Muthu, Anjali Roy, Uzma Saqib, Adnan Naim, Syed M Faisal, Mansi Srivastava, Rohit Saluja
Inflammation could be described as a physiological response of the body to tissue injury, pathogen invasion, and irritants. During the inflammatory phase, cells of both the innate as well as adaptive immune system are activated and recruited to the site of inflammation. These mediators are downstream targets for the transcription factors; activator protein-1 (AP1), nuclear factor kappa-light-chain-enhancer (NF-κB), signal transducers and activators of transcription factors (STAT1), as well as interferon regulatory factors (IRFs), which control the expression of most immunomodulatory genes...
May 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28527896/molecular-characterization-and-expression-analyses-of-the-solea-senegalensis-interferon-stimulated-gene-15-isg15-following-nnv-infections
#13
Daniel Álvarez-Torres, Ana María Podadera, M Carmen Alonso, Isabel Bandín, Julia Béjar, Esther García-Rosado
Interferons are essential in fish resistance to viral infections. They induce interferon-stimulated genes, such as isg15. In this study, the Senegalese sole isg15 gene (ssisg15) has been characterized. As other isg15, ssisg15 contains a 402-bp intron sited in the 5'-UTR, and the full length cDNA is 1492-bp, including a 480-bp ORF. The expression analyses revealed basal levels of isg15 transcripts, and a clear induction after poly I:C injection, that reached maximum values in brain, head kidney and gills. The ssisg15 induction patterns were similar in RGNNV- and SJNNV-inoculated fish, whereas the reassortant (RG/SJ) isolate, which has higher replication fitness, triggered delayed but higher transcript levels...
May 17, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28523924/comparison-of-transcriptional-profiles-of-interferons-cxcl10-and-rig-1-in-influenza-infected-a549-cells-stimulated-with-exogenous-interferons
#14
V Lachová, L Škorvanová, D Svetlíková, L Turianová, A Kostrábová, T Betáková
Type I and type III interferons (IFNs) are induced by viral infection. It was concluded that these IFN species are identical in regulation and biological functions. However, these two systems differ in the tissue expression of their receptors and their transcriptional regulation is fundamentally different as well as cellular signaling pathways that drive expression of each IFN. Here, we have investigated the transcriptional profile of endogenous IFNs after stimulation of cells with exogenous IFNs and subsequent infection of A549 cells with A/chicken/Germany/27 [H7N7] influenza virus...
2017: Acta Virologica
https://www.readbyqxmd.com/read/28522827/involvement-of-gata1-and-sp3-in-the-activation-of-the-murine-sting-gene-promoter-in-nih3t3-cells
#15
Yan-Yan Xu, Rui Jin, Guo-Ping Zhou, Hua-Guo Xu
Stimulator of Interferon Gene (STING) is a key mediator of innate immune signaling. STING plays a pivotal role in the pathogenesis of many diseases including infectious diseases, auto-immune diseases and cancer. Many studies have been carried out recently in the field of STING-regulated pathway, however, rarely of transcriptional mechanisms. To characterize the murine STING (mSTING) promoter, we cloned a series of different nucleotide sequences of the 5'-flanking region of the mSTING gene. Transient transfection of promoter-reporter recombinant plasmids and luciferase assay illustrated the region (-77/+177) relative to the transcription start site (TSS) of the mSTING gene was sufficient for full promoter activity...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28520587/complementary-roles-of-nod2-in-hematopoietic-and-nonhematopoietic-cells-in-preventing-gut-barrier-dysfunction-dependent-on-mlck-activity
#16
Ziad Al Nabhani, Nicolas Montcuquet, Maryline Roy, Monique Dussaillant, Jean-Pierre Hugot, Frédérick Barreau
BACKGROUND: Crohn's disease (CD) pathogenesis is multifactorial involving genetic and environmental factors. Loss of function mutations in the nucleotide oligomerization domain 2 (NOD2) gene are the main genetic risk factor for CD. Like patients with CD, Nod2 mice are characterized by an enhanced Th1 immune response and a defective mucosal barrier function evidenced by increased intestinal permeability. We previously showed that the latter is related to hematopoietic Nod2 deficiency. Our aim was to explore the mechanisms by which Nod2 expressed in the hematopoietic and in the nonhematopoietic compartments interplay to control epithelial paracellular permeability...
May 16, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28519900/type-i-interferon-pathway-in-cns-homeostasis-and-neurological-disorders
#17
REVIEW
Thomas Blank, Marco Prinz
Type I interferons (IFNs), IFN-α and IFN-β, represent the major effector cytokines of the host immune response against viruses and other intracellular pathogens. These cytokines are produced via activation of numerous pattern recognition receptors, including the Toll-like receptor signaling network, retinoic acid-inducible gene-1 (RIG-1), melanoma differentiation-associated protein-5 (MDA-5) and interferon gamma-inducible protein-16 (IFI-16). Whilst the contribution of type I IFNs to peripheral immunity is well documented, they can also be produced by almost every cell in the central nervous system (CNS)...
May 18, 2017: Glia
https://www.readbyqxmd.com/read/28514196/interactions-between-ns1-of-influenza-a-viruses-and-interferon-%C3%AE-%C3%AE-determinants-for-vaccine-development
#18
Ben X Wang, Eleanor N Fish
Influenza A viruses (IAVs) cause mild to severe infections in humans with considerable socioeconomic and global health consequences. The host interferon (IFN)-α/β response, critical as the first line of defense against foreign pathogens, is induced upon detection of IAV genomic RNA in infected cells by host innate pattern recognition receptors. IFN-α/β production and subsequent activation of cell signaling result in the expression of antiviral IFN-stimulated genes whose products target various stages of the IAV life cycle to inhibit viral replication and the spread of infection and establish an antiviral state...
May 17, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28507808/pro-necrotic-molecules-impact-local-immunosurveillance-in-human-breast-cancer
#19
Gautier Stoll, Yuting Ma, Heng Yang, Oliver Kepp, Laurence Zitvogel, Guido Kroemer
Necrosis culminates in spilling cellular content through the permeabilized plasma membrane, thereby releasing potentially immunostimulatory molecules in the pericellular space of dead cells. Accordingly, molecules involved in necroptotic signaling, such as receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and mixed lineage kinase-like (MLKL) have been found to stimulate anticancer immune responses in mouse models of chemotherapy. mRNAs encoding prominent pro-necrotic gene products (RIPK1, RIPK3, MLKL, PGAM5 and DFNA5) were correlated with immune-related metagenes in several cancer types (breast, colorectal, lung, ovary, melanoma), revealing the strongest associations in breast cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507795/digital-analysis-and-epigenetic-regulation-of-the-signature-of-rejection-in-colorectal-cancer
#20
Viktor H Koelzer, Lena Sokol, Stefan Zahnd, Lucine Christe, Heather Dawson, Martin D Berger, Daniel Inderbitzin, Inti Zlobec, Alessandro Lugli
The immune system plays a pivotal role in the development and progression of colorectal cancer (CRC). Tumor immune rejection has been previously linked to the activation of the interferon-stimulated genes (ISG) STAT1, IRF-5 and IRF-1. Specific immunoregulatory microRNAs (miRNAs) may impact the expression of these ISG in the tumor microenvironment. In this translational study, we develop a digital image analysis protocol to identify the ISG-gene expression signature and investigate miRNA expression in the immediate environment of invading cancer cells...
2017: Oncoimmunology
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