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https://www.readbyqxmd.com/read/29769346/porcine-deltacoronavirus-accessory-protein-ns6-antagonizes-ifn-%C3%AE-production-by-interfering-with-the-binding-of-rig-i-mda5-to-double-stranded-rna
#1
Puxian Fang, Liurong Fang, Jie Ren, Yingying Hong, Xiaorong Liu, Yunyang Zhao, Dang Wang, Guiqing Peng, Shaobo Xiao
Porcine deltacoronavirus (PDCoV) has recently emerged as an enteric pathogen that can cause serious vomiting and diarrhea in suckling piglets. The first outbreak of PDCoV occurred in the United States in 2014 and was followed by reports of PDCoV in South Korea, China, Thailand, Lao people's Democratic Republic, and Vietnam, leading to economic losses for pig farms and posing considerable threat to the swine industry worldwide. Our previous studies have shown that PDCoV encodes three accessory proteins, NS6, NS7, and NS7a, but the functions of these proteins in viral replication, pathogenesis, and immune regulation remain unclear...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29765321/brain-lipopolysaccharide-preconditioning-induced-gene-reprogramming-mediates-a-tolerance-state-in-electroconvulsive-shock-model-of-epilepsy
#2
Elham Amini, Mojtaba Golpich, Abdoreza S Farjam, Behnam Kamalidehghan, Zahurin Mohamed, Norlinah M Ibrahim, Abolhassan Ahmadiani, Azman A Raymond
There is increasing evidence pointing toward the role of inflammatory processes in epileptic seizures, and reciprocally, prolonged seizures induce more inflammation in the brain. In this regard, effective strategies to control epilepsy resulting from neuroinflammation could be targeted. Based on the available data, preconditioning (PC) with low dose lipopolysaccharide (LPS) through the regulation of the TLR4 signaling pathway provides neuroprotection against subsequent challenge with injury in the brain. To test this, we examined the effects of a single and chronic brain LPS PC, which is expected to lead to reduction of inflammation against epileptic seizures induced by electroconvulsive shock (ECS)...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29760187/lipopolysaccharide-lps-binding-protein-stimulates-cd14-dependent-toll-like-receptor-4-internalization-and-lps-induced-tbk1-ikk%C3%AF%C2%B5-irf3-axis-activation
#3
Hiroki Tsukamoto, Shino Takeuchi, Kanae Kubota, Yohei Kobayashi, Sao Kozakai, Ippo Ukai, Ayumi Shichiku, Misaki Okubo, Muneo Numasaki, Yoshitomi Kanemitsu, Yotaro Matsumoto, Tomonori Nochi, Kouichi Watanabe, Hisashi Aso, Yoshihisa Tomioka
Toll-like receptor 4 (TLR4) is an indispensable immune receptor for lipopolysaccharide (LPS), a major component of the Gram-negative bacterial cell wall. Following LPS stimulation, TLR4 transmits the signal from the cell surface and becomes internalized in an endosome. However, the spatial regulation of TLR4 signaling is not fully understood. Here, we investigated the mechanisms of LPS-induced TLR4 internalization and clarified the roles of the extracellular LPS-binding molecules, LPS-binding protein (LBP), and glycerophosphatidylinositol-anchored protein (CD14)...
May 14, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29755465/irf3-negatively-regulates-toll-like-receptor-mediated-nf-%C3%AE%C2%BAb-signaling-by-targeting-trif-for-degradation-in-teleost-fish
#4
Xueyan Zhao, Ruixuan Huo, Xiaolong Yan, Tianjun Xu
NF-κB signaling is tightly regulated and essential to innate and adaptive immune responses, its regulatory mechanism remains unclear in various organisms, especially teleosts. In this study, we reported that IRF3 can negatively regulate TRIF-mediated NF-κB signaling pathway. Overexpression of IRF3 can inhibit TRIF-mediated NF-κB signaling pathway. However, knockdown of IRF3 had an opposite effect. IRF3 can promote the degradation of TRIF protein in mammal and fish cells, but this effect could be inhibited by MG132 treatment...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29755463/the-role-of-optineurin-in-antiviral-type-i-interferon-production
#5
REVIEW
Ahmed Outlioua, Marie Pourcelot, Damien Arnoult
After a viral infection and the stimulation of some pattern-recognition receptors as the toll-like receptor 3 in the endosomes or the RIG-I-like receptors in the cytosol, activation of the IKK-related kinase TBK1 leads to the production of type I interferons (IFNs) after phosphorylation of the transcription factors IRF3 and IRF7. Recent findings indicate an involvement of K63-linked polyubiquitination and of the Golgi-localized protein optineurin (OPTN) in the activation of this crucial kinase involved in innate antiviral immunity...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29753769/fish-samhd1-performs-as-an-activator-for-ifn-expression
#6
Meifeng Li, Xiaowen Xu, Zeyin Jiang, Changxin Liu, Xiao Shi, Guoqin Qi, Yinping Li, Xin Chen, Qingli Huang, Huiling Mao, Chengyu Hu
As a host limiting factor, Sterile Alpha Motif and Histidine-Aspartate Domain 1 protein (SAMHD1) is associated with IRF3-mediated antiviral and apoptotic responses in mammals. However, the antiviral mechanism of SAMHD1 remains indistinct in fish. In this study, we found the expression of Ctenopharyngodon idella SAMHD1 (MF326081) was up-regulated after transfection with poly I:C (dsRNA analog), B-DNA or Z-DNA into C. idella kidney cells (CIKs), but these expression profiles had no obvious change when the cells were incubated with these nucleic acids...
May 10, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29735480/comparative-transcriptomic-response-of-primary-and-immortalized-macrophage-to-murine-norovirus-infection
#7
Eric A Levenson, Craig Martens, Kishore Kanakabandi, Charles V Turner, Kimmo Virtaneva, Monica Paneru, Stacy Ricklefs, Stanislav V Sosnovtsev, Jordan A Johnson, Stephen F Porcella, Kim Y Green
Murine norovirus (NoV) is genetically similar to human NoV and offers both an efficient in vitro cell culture system and an animal model by which to investigate the molecular basis of replication. In this study, we present a detailed global view of host alterations to cellular pathways that occur during the progression of a NoV infection. This was accomplished for both Mus musculus BALB/c-derived RAW264.7 (RAW) cells, an immortalized cell line widely used in in vitro replication studies, and primary bone marrow-derived macrophages (BMDM), representing a permissive in vivo target cell in the host...
May 7, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29733958/protein-a-from-orange-spotted-nervous-necrosis-virus-triggers-type-i-interferon-production-in-fish-cell
#8
Runqing Huang, Qiong Zhou, Yan Shi, Jing Zhang, Jianguo He, Junfeng Xie
Family Nodaviridae consists of two genera: Alphanodavirus and Betanodavirus, and the latter is classified into four genotypes, including red-spotted grouper nervous necrosis virus, tiger puffer nervous necrosis virus, striped jack nervous necrosis virus, and barfin flounder nervous necrosis virus. Type I interferons (IFNs) play a central role in the innate immune system and antiviral responses, and the interactions between IFN and NNV have been investigated in this study. We have found that the RNA-dependent RNA polymerase (RdRp) from orange-spotted nervous necrosis virus (OGNNV), named protein A, was capable of activating IFN promoter in fathead minnow (FHM) cells...
May 4, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29732997/hydroxysafflor-yellow-a-reprograms-tlr9-signalling-pathway-in-ischaemic-cortex-after-cerebral-ischaemia-and-reperfusion
#9
Zhe Gong, Jingrui Pan, Xiangpen Li, Hongxuan Wang, Lei He, Ying Peng
Hydroxysafflor yellow A (HSYA) was reported to suppress inflammation in ischaemic microglia. However, the mechanism through which HSYA inhibits inflammation caused by cerebral ischaemia and reperfusion injury remains unknown. Here, we have mimicked acute cerebral ischaemia and reperfusion injury by subjecting male Sprague-Dawley (SD) rats to transient middle cerebral artery occlusion for 90 minutes and have demonstrated that toll-like receptor 9 (TLR9) was upregulated from day 3 after reperfusion, accompanied by the persistent activation of the pro-inflammatory NF-κB pathway from 6 hours to day 7...
May 1, 2018: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/29727627/differential-interferon-system-gene-expression-profiles-in-susceptible-and-resistant-gynogenetic-clones-of-gibel-carp-challenged-with-herpesvirus-cahv
#10
Cheng-Yan Mou, Yang Wang, Qi-Ya Zhang, Fan-Xiang Gao, Zhi Li, Jin-Feng Tong, Li Zhou, Jian-Fang Gui
Interferon (IFN) system plays a vital role in the first line of defense against viruses. In this study, we first identified multiple transcripts of 15 IFN system genes, including PRRs (TLR2, TLR3, RIG-I, and LGP2), PRR-mediated IFN signal pathway (MyD88, MITA, and MAVS), IFN regulatory factors (IRF1, IRF3, IRF7, and IRF9), IFNs (IFNφ1 and IFNφ3), and ISGs (Mx and viperin), and one transcript of TLR9 in de novo transcriptome assembly data of gibel carp head-kidney. Multiple nucleotide alignments and phylogenetic analysis of common region showed that the transcripts of every of the 15 IFN system genes were classified into two homologs with distinctly divergent sequences, indicating that hexaploid gibel carp may be an allopolyploid...
May 1, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29721392/bufalin-suppresses-migration-and-invasion-of-hepatocellular-carcinoma-cells-elicited-by-poly-i-c-therapy
#11
Yinglu Feng, Yongan Chen, Yongbin Meng, Qingxin Cao, Qun Liu, Changquan Ling, Chen Wang
The Toll-like receptor 3 (TLR3) agonists as polyriboinosinic-polyribocytidylic acid (poly (I:C)) have been implicated as potential immunotherapy adjuvant for cancer whereas the exact roles of TLR3 agonists in hepatocellular carcinoma (HCC) treatment have not been clearly evaluated. In consistent with previous reports, we found that poly (I:C) triggering of TLR3 inhibited cell proliferation and induced apoptosis in HCC cells. However, poly (I:C), when used at lower concentration that cannot remarkably inhibit proliferation and induce apoptosis in HCC cells, enhanced the migration and invasion in vitro and the metastasis in vivo...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29720400/interferon-regulatory-factor-1-and-a-variant-of-heterogeneous-nuclear-ribonucleoprotein-l-coordinately-silence-the-gene-for-adhesion-protein-ceacam1
#12
Kenneth J Dery, Craig Silver, Lu Yang, John E Shively
The adhesion protein Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is widely expressed in epithelial cells as a short cytoplasmic isoform (S-iso) and in leukocytes as a long cytoplasmic isoform (L-iso) and is frequently silenced in cancer by unknown mechanisms. Previously, we reported that interferon response factor 1 (IRF1) biases alternative splicing (AS) to include the variable exon 7 in CEACAM1, generating L-iso. We now show that IRF1 and a variant of heterogeneous nuclear ribonucleoprotein L (Lv1) coordinately silence the CEACAM1 gene...
May 2, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29720226/increased-a20-e3-ubiquitin-ligase-interactions-in-bid-deficient-glia-attenuate-tlr3-and-tlr4-induced-inflammation
#13
Sinéad Kinsella, Michael Fichtner, Orla Watters, Hans-Georg König, Jochen H M Prehn
BACKGROUND: Chronic pro-inflammatory signaling propagates damage to neural tissue and affects the rate of disease progression. Increased activation of Toll-like receptors (TLRs), master regulators of the innate immune response, is implicated in the etiology of several neuropathologies including amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease. Previously, we identified that the Bcl-2 family protein BH3-interacting domain death agonist (Bid) potentiates the TLR4-NF-κB pro-inflammatory response in glia, and specifically characterized an interaction between Bid and TNF receptor associated factor 6 (TRAF6) in microglia in response to TLR4 activation...
May 2, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29712834/revisiting-the-role-of-irf3-in-inflammation-and-immunity-by-conditional-and-specifically-targeted-gene-ablation-in-mice
#14
Hideyuki Yanai, Shiho Chiba, Sho Hangai, Kohei Kometani, Asuka Inoue, Yoshitaka Kimura, Takaya Abe, Hiroshi Kiyonari, Junko Nishio, Naoko Taguchi-Atarashi, Yu Mizushima, Hideo Negishi, Rudolf Grosschedl, Tadatsugu Taniguchi
IFN regulatory factor 3 (IRF3) is a transcription regulator of cellular responses in many cell types that is known to be essential for innate immunity. To confirm IRF3's broad role in immunity and to more fully discern its role in various cellular subsets, we engineered Irf3 -floxed mice to allow for the cell type-specific ablation of Irf3 Analysis of these mice confirmed the general requirement of IRF3 for the evocation of type I IFN responses in vitro and in vivo. Furthermore, immune cell ontogeny and frequencies of immune cell types were unaffected when Irf3 was selectively inactivated in either T cells or B cells in the mice...
April 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29681974/baicalin-downregulates-rlrs-signaling-pathway-to-control-influenza-a-virus-infection-and-improve-the-prognosis
#15
Peng Pang, Ke Zheng, Sizhi Wu, Huachong Xu, Li Deng, Yucong Shi, Xiaoyin Chen
The objective of this study is to investigate the effects of baicalin on controlling the pulmonary infection and improving the prognosis in influenza A virus (IAV) infection. PCR and western blot were used to measure the changes of some key factors in RLRs signaling pathway. MSD electrochemiluminescence was used to measure the expression of pulmonary inflammatory cytokines including IFN- γ , TNF- α , IL-1 β , IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, and KC/GRO. Flow cytometry was used to detect the proportion of Th1, Th2, Th17, and Treg...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29678949/hu-antigen-r-regulates-antiviral-innate-immune-responses-through-the-stabilization-of-mrna-for-polo-like-kinase-2
#16
Takuya Sueyoshi, Takumi Kawasaki, Yuichi Kitai, Daisuke Ori, Shizuo Akira, Taro Kawai
Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), RIG-I, and melanoma differentiation-associated gene 5 (MDA5) play a critical role in inducing antiviral innate immune responses by activating IFN regulatory factor 3 (IRF3) and NF-κB, which regulates the transcription of type I IFN and inflammatory cytokines. Antiviral innate immune responses are also regulated by posttranscriptional and translational mechanisms. In this study, we identified an RNA-binding protein HuR as a regulator for RLR signaling...
April 20, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29677136/cytoplasmic-translocation-of-nucleolar-protein-nop53-promotes-viral-replication-by-suppressing-host-defense
#17
Wen Meng, Shi-Chong Han, Cui-Cui Li, Hui-Jun Dong, Jian-Yu Chang, Hwa-Chain Robert Wang, Xiao-Jia Wang
NOP53 is a tumor suppressor protein located in the nucleolus and is translocated to the cytoplasm during infection by vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1), as shown in our previous study. Cytoplasmic NOP53 interacts with the retinoic acid-inducible gene I (RIG-I) to remove its K63-linked ubiquitination, leading to attenuation of type I interferon IFN-β. In the present study, we found no obvious translocation of NOP53 in infection by a mutant virus lacking ICP4 (HSV-1/d120, replication inadequate)...
April 20, 2018: Viruses
https://www.readbyqxmd.com/read/29673738/tbk1-a-key-regulator-and-potential-treatment-target-for-interferon-positive-sj%C3%A3-gren-s-syndrome-systemic-lupus-erythematosus-and-systemic-sclerosis
#18
Iris L A Bodewes, Erika Huijser, Cornelia G van Helden-Meeuwsen, Liselotte Tas, Ruth Huizinga, Virgil A S H Dalm, P Martin van Hagen, Noortje Groot, Sylvia Kamphuis, Paul L A van Daele, Marjan A Versnel
OBJECTIVE: Upregulation of type I interferons (IFN-I) is a hallmark of systemic autoimmune diseases like primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Expression of IFN-I is induced by three different receptor families: Toll-like receptors (TLRs), RIG-like receptors (RLRs) and DNA-sensing receptors (DSRs). TANK-binding kinase (TBK1) is an important signaling hub downstream of RLRs and DSRs. TBK1 activates IRF3 and IRF7, leading to IFN-I production and subsequent induction of interferon stimulated genes (ISGs)...
April 16, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29661858/rna-sensor-lgp2-inhibits-traf-ubiquitin-ligase-to-negatively-regulate-innate-immune-signaling
#19
Jean-Patrick Parisien, Jessica J Lenoir, Roli Mandhana, Kenny R Rodriguez, Kenin Qian, Annie M Bruns, Curt M Horvath
The production of type I interferon (IFN) is essential for cellular barrier functions and innate and adaptive antiviral immunity. In response to virus infections, RNA receptors RIG-I and MDA5 stimulate a mitochondria-localized signaling apparatus that uses TRAF family ubiquitin ligase proteins to activate master transcription regulators IRF3 and NFκB, driving IFN and antiviral target gene expression. Data indicate that a third RNA receptor, LGP2, acts as a negative regulator of antiviral signaling by interfering with TRAF family proteins...
April 16, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29658082/effect-of-oxidized-dextran-on-cytokine-production-and-activation-of-irf3-transcription-factor-in-macrophages-from-mice-of-opposite-strains-with-different-sensitivity-to-tuberculosis-infection
#20
A V Chechushkov, P M Kozhin, N S Zaitseva, P I Gainutdinov, E B Men'shchikova, A V Troitskii, V A Shkurupy
We studied differences in the production of pro- and anti-inflammatory cytokines and IRF3 transcription factor by peritoneal macrophages from mice of opposite strains CBA/J and C57Bl/6 and the effect of 60-kDa oxidized dextran on these parameters. Macrophages from C57Bl/6 mice were mainly characterized by the production of proinflammatory cytokines TNFα, IL-12, and MCP-1 (markers of M1 polarization). By contrast, CBA/J mice exhibited a relatively high level of anti-inflammatory cytokine IL-10 and lower expression of proinflammatory cytokines (M2 phenotype)...
April 2018: Bulletin of Experimental Biology and Medicine
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