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https://www.readbyqxmd.com/read/28904192/the-role-of-herpes-simplex-virus-type-1-%C3%AE-34-5-in-the-regulation-of-irf3-signaling
#1
Richard Manivanh, Jesse Mehrbach, David M Knipe, David A Leib
During viral infection, pattern recognition receptors (PRRs) and their associated adaptors recruit TANK-binding kinase 1 (TBK1) to activate interferon regulatory factor 3 (IRF3), resulting in production of type I interferons (IFNs). ICP0 and ICP34.5 are amongst the proteins encoded by herpes simplex virus 1 (HSV-1) that modulate type I IFN signaling. We constructed a recombinant virus (ΔXX) which lacks amino acids 87 - 106, a portion of the previously described TBK1-binding domain of the γ34.5 gene (D. Verpooten, Y...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28898711/sjl-bone-marrow-derived-macrophages-do-not-have-irf3-mutations-and-are-highly-susceptible-to-theiler-s-virus-infection
#2
Kyung-No Son, Zhiguo Liang, Howard L Lipton
It is well known that SJL mice are susceptible to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease while C57BL6 (B6) and B10 mice are resistant, and H-2(s) on a B10 background (B10.S) contributes modestly to susceptibility. A recent study linked two IRF3 non-conservative mutations in SJL compared to B10.S mice to resistance to TMEV infection of SJL peritoneal-derived macrophages, an observation of practical interest in light of the central role of IRF3 transcription factor in the type I interferon (IFN) response...
September 9, 2017: Virology
https://www.readbyqxmd.com/read/28890139/duck-interferon-regulatory-factor-1-acts-as-a-positive-regulator-in-duck-innate-antiviral-response
#3
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
#4
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/28883758/hydroquinone-suppresses-ifn-%C3%AE-expression-by-targeting-akt-irf3-pathway
#5
Yong Kim, Han Gyung Kim, Sang Yun Han, Deok Jeong, Woo Seok Yang, Jung-Il Kim, Ji Hye Kim, Young-Su Yi, Jae Youl Cho
Previous studies have demonstrated the role of hydroquinone (HQ), a hydroxylated benzene metabolite, in modulating various immune responses; however, its role in macrophage-mediated inflammatory responses is not fully understood. In this study, the role of HQ in inflammatory responses and the underlying molecular mechanism were explored in macrophages. HQ down-regulated the expression of interferon (IFN)-β mRNA in LPS-stimulated RAW264.7 cells without any cytotoxicity and suppressed interferon regulatory factor (IRF)-3-mediated luciferase activity induced by TIR-domain-containing adapter-inducing interferon-β (TRIF) and TANK-binding kinase 1 (TBK1)...
September 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28883463/reovirus-inhibits-interferon-production-by-sequestering-irf3-into-viral-factories
#6
Megan L Stanifer, Christian Kischnick, Anja Rippert, Dorothee Albrecht, Steeve Boulant
Upon viral infection, an arms-race between the cellular intrinsic innate immune system and viral replication is established. To win this race, viruses have established multiple strategies to inhibit the cellular response. Mammalian reovirus (MRV) constitutes a great model to study pathogenesis and life cycle of dsRNA viruses. It replicates in the cytosol of infected cells by forming viral induced-replication compartments, or viral factories. Little is known about the strategy used by MRV to evade the cellular intrinsic immune system...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28878071/zika-virus-escapes-nk-cell-detection-by-upregulating-mhc-class-i-molecules
#7
Ariella Glasner, Esther Oiknine-Djian, Yiska Weisblum, Mohammad Diab, Amos Panet, Dana G Wolf, Ofer Mandelboim
NK cells are innate lymphocytes that participate in many immune processes encompassing cancer, bacterial and fungal infection, autoimmunity and even pregnancy and are specialize in anti-viral defense. NK cells express inhibitory and activating receptors and kill their targets when activating signals overpower the inhibitory ones. The NK cell inhibitory receptors compose of a uniquely diverse array of proteins named Killer-cell immunoglobulin-like receptors (KIRs) the CD94 family and the leukocyte immunoglobulin like receptor family (LIR)...
September 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28874755/spi-2-crma-inhibits-ifn-%C3%AE-induction-by-targeting-tbk1-ikk%C3%AE%C2%B5
#8
Yue Qin, Mi Li, Sheng-Long Zhou, Wei Yin, Zhuan Bian, Hong-Bing Shu
Viruses modulate the host immune system to evade host antiviral responses. The poxvirus proteins serine proteinase inhibitor 2 (SPI-2) and cytokine response modifier A (CrmA) are involved in multiple poxvirus evasion strategies. SPI-2 and CrmA target caspase-1 to prevent apoptosis and cytokine activation. Here, we identified SPI-2 and CrmA as negative regulators of virus-triggered induction of IFN-β. Ectopic expression of SPI-2 or CrmA inhibited virus-triggered induction of IFN-β and its downstream genes...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28870522/poly-i-c-impairs-no-donor-induced-relaxation-by-overexposure-to-no-via-the-nf-kappa-b-inos-pathway-in-rat-superior-mesenteric-arteries
#9
Makoto Ando, Takayuki Matsumoto, Kumiko Taguchi, Tsuneo Kobayashi
Recent studies have suggested a link between vascular dysfunction and innate immune activation including toll-like receptors (TLRs), but the detailed mechanism remains unclear. Here we investigated whether poly (I:C) [a synthetic double-strand RNA recognized by TLR3, melanoma differentiation-associated gene 5 (MDA5), and retinoic acid-inducible gene I (RIG-I)] affected nitric oxide (NO)/cGMP-related vascular relaxation, one of the major cascades of relaxation, in rat superior mesenteric arteries. Using organ-cultured arteries, we found that poly (I:C) (30μg/mL for approximately 1 day) markedly reduced sodium nitroprusside (SNP)-induced relaxation (vs...
September 1, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28865677/berkeleyacetal-c-a-meroterpenoid-isolated-from-the-fungus-penicilium-purpurogenum-mhz-111-exerts-anti-inflammatory-effects-via-inhibiting-nf-%C3%AE%C2%BAb-erk1-2-and-irf3-signaling-pathways
#10
Shan-Shan Li, Jun Li, Jing Sun, Ran Guo, Lan-Zhi Yu, Yun-Fang Zhao, Zhi-Xiang Zhu, Peng-Fei Tu
Berkeleyacetal C (BAC), a meroterpenoid compound, was isolated from the fungus Penicillium purpurogenum MHZ 111 and showed favorable activity of inhibiting nitrogen oxide (NO) production of macrophages stimulated by lipopolysaccharide (LPS) in our preliminary screening. In order to develop novel therapeutic drug for acute and chronic inflammatory diseases, the anti-inflammatory activity and underlying mechanisms of BAC were investigated in macrophages and neutrophils. The results showed that BAC significantly inhibited the expression of inducible nitric oxide synthase (iNOS) and the following NO production by macrophages...
August 30, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28859978/carbonyl-cyanide-3-chlorophenylhydrazone-cccp-suppresses-sting-mediated-dna-sensing-pathway-through-inducing-mitochondrial-fission
#11
Dohyeong Kwon, Eunbyeol Park, Hiromi Sesaki, Suk-Jo Kang
Besides its important role in innate immune response to DNA virus infection, the regulatory function of STING in autoimmunity and cancer is emerging. Recently, multiple mechanisms regulating the activity of the STING pathway have been revealed. Previous study showed that carbonyl cyanide 3-chlorophenylhydrazone (CCCP), the protonophore, inhibited STING-mediated IFN-β production via disrupting mitochondrial membrane potential (MMP). However, how MMP dissipation leads to the suppression of the STING pathway remains unknown...
August 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28857295/a-protective-role-of-irf3-and-irf7-signaling-downstream-tlrs-in-the-development-of-vein-graft-disease-via-type-i-interferons
#12
K H Simons, H A B Peters, J Wouter Jukema, M R de Vries, P H A Quax
BACKGROUND: Toll like receptors (TLR) play an important role in vein graft disease (VGD). Interferon regulatory factors (IRF) 3 and 7 are the transcriptional regulators of type-I interferons (IFN) and type-I IFN responsive genes and are downstream factors of TLRs. Relatively little is known with regard to the interplay of IRFs and TLRs in VGD development. The aim of this study was to investigate the role of IRF3 and IRF7 signaling downstream TLRs and the effect of IRF3 and IRF7 in VGD...
August 31, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28854793/nss-protein-of-severe-fever-with-thrombocytopenia-syndrome-virus-suppresses-interferon-production-through-different-mechanism-than-rift-valley-fever-virus
#13
S Zhang, B Zheng, T Wang, A Li, J Wan, J Qu, C H Li, D Li, M Liang
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly identified Phlebovirus that causes severe fever with thrombocytopenia syndrome. Our study demonstrated that SFTSV NSs functioned as IFN antagonist mainly by suppressing TBK1/IKKε-IRF3 signaling pathway. NSs interacted with and relocalized TANK-binding kinase 1 (TBK1) into NSs-induced cytoplasmic structures and this interaction could effectively inhibit downstream phosphorylation and dimerization of interferon regulatory factor 3 (IRF3), resulting in the suppression of antiviral signaling and IFN induction...
2017: Acta Virologica
https://www.readbyqxmd.com/read/28854257/hrs-plays-an-important-role-for-tlr7-signaling-to-orchestrate-inflammation-and-innate-immunity-upon-ev71-infection
#14
Zhen Luo, Maolin Ge, Junbo Chen, Qibin Geng, Mingfu Tian, Zhi Qiao, Lan Bai, Qi Zhang, Chengliang Zhu, Ying Xiong, Kailang Wu, Fang Liu, Yingle Liu, Jianguo Wu
Enterovirus 71 (EV71) is an RNA virus that causes hand-foot-mouth disease (HFMD), and even fatal encephalitis in children. Although EV71 pathogenesis remains largely obscure, host immune responses may play important roles in the development of diseases. Recognition of pathogens mediated by Toll-like receptors (TLRs) induces host immune and inflammatory responses. Intracellular TLRs must traffic from the endoplasmic reticulum (ER) to the endolysosomal network from where they initiate complete signaling, leading to inflammatory response...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28831401/global-screening-of-antiviral-genes-that-suppress-baculovirus-transgene-expression-in-mammalian-cells
#15
Chia-Hung Wang, Nenavath Gopal Naik, Lin-Li Liao, Sung-Chan Wei, Yu-Chan Chao
Although baculovirus has been used as a safe and convenient gene delivery vector in mammalian cells, baculovirus-mediated transgene expression is less effective in various mammalian cell lines. Identification of the negative regulators in host cells is necessary to improve baculovirus-based expression systems. Here, we performed high-throughput shRNA library screening, targeting 176 antiviral innate immune genes, and identified 43 host restriction factor genes in a human A549 lung carcinoma cell line. Among them, suppression of receptor interaction protein kinase 1 (RIP1, also known as RIPK1) significantly increased baculoviral transgene expression without resulting in significant cell death...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28827286/anti-cancer-drug-hmba-acts-as-an-adjuvant-during-intracellular-bacterial-infections-by-inducing-type-i-ifn-through-sting
#16
Akshamal Mihiranga Gamage, Kok-Onn Lee, Yunn-Hwen Gan
The anti-proliferative agent hexamethylene bisacetamide (HMBA) belongs to a class of hybrid bipolar compounds developed more than 30 y ago for their ability to induce terminal differentiation of transformed cells. Recently, HMBA has also been shown to trigger HIV transcription from latently infected cells, via a CDK9/HMBA inducible protein-1 dependent process. However, the effect of HMBA on the immune response has not been explored. We observed that pretreatment of human peripheral blood mononuclear cells with HMBA led to a markedly increased production of IL-12 and IFN-γ, but not of TNF-α, IL-6, and IL-8 upon subsequent infection with Burkholderia pseudomallei and Salmonella enterica HMBA treatment was also associated with better intracellular bacterial control...
August 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28818792/regulation-of-type-i-interferon-responses-by-mitochondria-derived-reactive-oxygen-species-in-plasmacytoid-dendritic-cells
#17
Zsofia Agod, Tünde Fekete, Marietta M Budai, Aliz Varga, Attila Szabo, Hyelim Moon, Istvan Boldogh, Tamas Biro, Arpad Lanyi, Attila Bacsi, Kitti Pazmandi
Mitochondrial reactive oxygen species (mtROS) generated continuously under physiological conditions have recently emerged as critical players in the regulation of immune signaling pathways. In this study we have investigated the regulation of antiviral signaling by increased mtROS production in plasmacytoid dendritic cells (pDCs), which, as major producers of type I interferons (IFN), are the key coordinators of antiviral immunity. The early phase of type I IFN production in pDCs is mediated by endosomal Toll-like receptors (TLRs), whereas the late phase of IFN response can also be triggered by cytosolic retinoic acid-inducible gene-I (RIG-I), expression of which is induced upon TLR stimulation...
July 29, 2017: Redox Biology
https://www.readbyqxmd.com/read/28802127/investigations-on-the-molecular-mode-of-action-of-the-novel-immunostimulator-zelnate-activation-of-the-cgas-sting-pathway-in-mammalian-cells
#18
Thomas Ilg
Bovine respiratory disease (BRD) is usually prevented or treated with vaccines and/or antibiotics. The use of antibiotics is, however, of concern due to the potential promotion of microbial resistance and the occurrence of residues. Recently an alternative aid in the treatment of BRD, the cationic lipid/bacterial plasmid DNA liposome-based immunomodulator ZelNate, has entered the veterinary market. In the present study, we provide data on the molecular mode of action of ZelNate. Despite the presence of numerous non-methylated CpG motifs in its plasmid DNA, ZelNate proved to be inactive on human and mouse toll-like receptor 9 (TLR9) in cell culture, in both recombinant and natural cellular receptor settings...
August 9, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28791644/analysis-of-constitutive-egfr-signaling-regulating-irf3-transcriptional-activity-in-cancer-cells
#19
Gao Guo, Ke Gong, Amyn A Habib
Epidermal growth factor receptor (EGFR) plays an important role in various types of human cancers. Overexpression of EGFR leads to a constitutive tyrosine phosphorylation of multiple tyrosine residues in the EGFR. Recently, we have demonstrated that overexpressed EGFR oscillates between two distinct and mutually exclusive modes of signaling depending on the presence or absence of ligand. EGFR constitutively activates transcription factor IRF3, which results in transcription of its target genes. Addition of EGF causes a loss of IRF3 transcriptional activity and activation of canonical signaling pathways such as ERK...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28790196/trif-dependent-toll-like-receptor-signaling-suppresses-scd1-transcription-in-hepatocytes-and-prevents-diet-induced-hepatic-steatosis
#20
Jing Chen, Jin Li, Jensen H C Yiu, Jenny K W Lam, Chi-Ming Wong, Bernhard Dorweiler, Aimin Xu, Connie W Woo
Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases that ranges in severity from hepatic steatosis to steatohepatitis, the latter of which is a major predisposing factor for liver cirrhosis and cancer. Toll-like receptor (TLR) signaling, which is critical for innate immunity, is generally believed to aggravate disease progression by inducing inflammation. Unexpectedly, we found that deficiency in TIR domain-containing adaptor-inducing interferon-β (TRIF), a cytosolic adaptor that transduces some TLR signals, worsened hepatic steatosis induced by a high-fat diet (HFD) and that such exacerbation was independent of myeloid cells...
August 8, 2017: Science Signaling
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