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https://www.readbyqxmd.com/read/29138248/usp1-uaf1-deubiquitinase-complex-stabilizes-tbk1-and-enhances-antiviral-responses
#1
Zhongxia Yu, Hui Song, Mutian Jia, Jintao Zhang, Wenwen Wang, Qi Li, Lining Zhang, Wei Zhao
Optimal activation of TANK-binding kinase 1 (TBK1) is crucial for initiation of innate antiviral immunity and maintenance of immune homeostasis. Although several E3 ubiquitin ligases have been reported to regulate TBK1 activation by mediating its polyubiquitination, the functions of deubiquitinase on TBK1 activity remain largely unclear. Here, we identified a deubiquitinase complex, which is formed by ubiquitin specific peptidase 1 (USP1) and USP1-associated factor 1 (UAF1), as a viral infection-induced physiological enhancer of TBK1 expression...
November 14, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29124042/e-fischeriana-root-compound-dpo-activates-antiviral-innate-immunity
#2
Jingxuan Chen, Hongqiang Du, Shuang Cui, Tong Liu, Guang Yang, Huaping Sun, Weiwei Tao, Baoping Jiang, Li Yu, Fuping You
E. fischeriana has long been used as a traditional Chinese medicine. Recent studies reported that some compounds of E. fischeriana exhibited antimicrobial and immune enhance activity. Innate immune system is essential for the immune surveillance of inner and outer threats, initial host defense responses and immune modulation. The role of natural drug compounds, including E. fischeriana, in innate immune regulation is largely unknown. Here we demonstrated that E. fischeriana compound Dpo is involved in antiviral signaling...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29117564/an-irf-3-irf-5-and-irf-7-independent-pathway-of-dengue-viral-resistance-utilizes-irf-1-to-stimulate-type-i-and-ii-interferon-responses
#3
Aaron F Carlin, Emily M Plummer, Edward A Vizcarra, Nicholas Sheets, Yunichel Joo, William Tang, Jeremy Day, Jay Greenbaum, Christopher K Glass, Michael S Diamond, Sujan Shresta
Interferon-regulatory factors (IRFs) are a family of transcription factors (TFs) that translate viral recognition into antiviral responses, including type I interferon (IFN) production. Dengue virus (DENV) and other clinically important flaviviruses are suppressed by type I IFN. While mice lacking the type I IFN receptor (Ifnar1(-/-)) succumb to DENV infection, we found that mice deficient in three transcription factors controlling type I IFN production (Irf3(-/-)Irf5(-/-)Irf7(-/-) triple knockout [TKO]) survive DENV challenge...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29113905/trim21-negatively-regulates-intestinal-mucosal-inflammation-through-inhibiting-th1-th17-cell-differentiation-in-inflammatory-bowel-diseases
#4
Guangxi Zhou, Wei Wu, Lin Yu, Tianming Yu, Wenjing Yang, Ping Wang, Xiaoping Zhang, Yingzi Cong, Zhanju Liu
BACKGROUND: Tripartite motif-containing (TRIM)21 has been implicated in pathogenesis of several types of autoimmune diseases. OBJECTIVE: We sought to elucidate expression of TRIM21 in patients with inflammatory bowel disease (IBD) and its role in regulating intestinal mucosal inflammation. METHODS: TRIM21 expression was analyzed in inflamed mucosa of IBD patients by qRT-PCR and immunohistochemistry. Peripheral blood CD4(+) T cells were transfected with lentivirus-expressing-TRIM21 (LV-TRIM21) or LV-sh-TRIM21, and cytokine expression was determined by qRT-PCR and ELISA...
November 4, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29107214/tim-3-enhances-brain-inflammation-by-promoting-m1-macrophage-polarization-following-intracerebral-hemorrhage-in-mice
#5
Anyong Yu, Xiaojun Zhang, Mo Li, Peng Ye, Haizhen Duan, Tianxi Zhang, Zhao Yang
Macrophage polarization contributes to brain inflammation following spontaneous intracerebral hemorrhage (ICH). T cell immunoglobulin and mucin domain-3 (Tim-3) has been identified to induce macrophage mediated inflammation following ICH. However, the regulation of Tim-3 on macrophage polarization following ICH has not been fully studied. In current experiment, we explored Tim-3 expression, macrophage polarization, brain water content and neurological function in WT and Tim-3(-)/(-) ICH mice. In addition, downstream transcriptional factor TRIF and IRF3 were also analyzed...
October 26, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29106945/activation-of-the-sting-irf3-pathway-promotes-hepatocyte-inflammation-apoptosis-and-induces-metabolic-disorders-in-nonalcoholic-fatty-liver-disease
#6
J T Qiao, C Cui, L Qing, L S Wang, T Y He, F Yan, F Q Liu, Y H Shen, X G Hou, L Chen
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a common result of obesity and metabolic syndrome. Hepatocyte injury and metabolic disorders are hallmarks of NAFLD. Stimulator of interferon genes (STING) and its downstream factor interferon regulatory factor 3 (IRF3) trigger inflammatory reaction in response to the presence of cytosolic DNA. STING has recently been shown to play an important role in early alcoholic liver disease. However, little is known about the role of STING-IRF3 pathway in hepatocyte injury...
October 26, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29106411/extrachromosomal-telomere-repeat-dna-is-linked-to-alt-development-via-cgas-sting-dna-sensing-pathway
#7
Yi-An Chen, Yi-Ling Shen, Hsuan-Yu Hsia, Yee-Peng Tiang, Tzu-Ling Sung, Liuh-Yow Chen
Extrachromosomal telomere repeat (ECTR) DNA is unique to cancer cells that maintain telomeres through the alternative lengthening of telomeres (ALT) pathway, but the role of ECTRs in ALT development remains elusive. We found that induction of ECTRs in normal human fibroblasts activated the cGAS-STING-TBK1-IRF3 signaling axis to trigger IFNβ production and a type I interferon response, resulting in cell-proliferation defects. In contrast, ALT cancer cells are commonly defective in sensing cytosolic DNA. We found that STING expression was inhibited in ALT cancer cell lines and transformed ALT cells...
November 6, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29106401/irf3-and-type-i-interferons-fuel-a-fatal-response-to-myocardial-infarction
#8
Kevin R King, Aaron D Aguirre, Yu-Xiang Ye, Yuan Sun, Jason D Roh, Richard P Ng, Rainer H Kohler, Sean P Arlauckas, Yoshiko Iwamoto, Andrej Savol, Ruslan I Sadreyev, Mark Kelly, Timothy P Fitzgibbons, Katherine A Fitzgerald, Timothy Mitchison, Peter Libby, Matthias Nahrendorf, Ralph Weissleder
Interferon regulatory factor 3 (IRF3) and type I interferons (IFNs) protect against infections and cancer, but excessive IRF3 activation and type I IFN production cause autoinflammatory conditions such as Aicardi-Goutières syndrome and STING-associated vasculopathy of infancy (SAVI). Myocardial infarction (MI) elicits inflammation, but the dominant molecular drivers of MI-associated inflammation remain unclear. Here we show that ischemic cell death and uptake of cell debris by macrophages in the heart fuel a fatal response to MI by activating IRF3 and type I IFN production...
November 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29102119/rig-1-and-mda-5-signaling-pathways-contribute-to-ifn-%C3%AE-production-and-viral-replication-in-porcine-circovirus-virus-type-2-infected-pk-15-cells-in-vitro
#9
Bei Huang, Jiansheng Li, Xinchen Zhang, Qiling Zhao, Mingqing Lu, Yingjun Lv
Type I Interferons (IFNs) is known for its antiviral activity; however, it is surprising that in vitro treatment of IFN-α and IFN-γ enhanced the replication of porcine circovirus type 2 (PCV2), indicating a complex relationship between interferon and PCV2. To date, it remains poorly understood how the interferon is produced during PCV2 infection and whether the interferon induced by PCV2 itself can promote viral replication. In this study, PCV2 induced the up-regulation of IFN-β in PK-15 cells, while treatment of PCV2-infected cells with the interferon regulatory factor-3 (IRF3) inhibitor, BX795, decreased the expression of IFN-β, whereas treatment with the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibitor, BAY11-7082, did not...
November 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/29101251/the-methyltransferase-nsd3-promotes-antiviral-innate-immunity-via-direct-lysine-methylation-of-irf3
#10
Chunmei Wang, Qinlan Wang, Xiaoqing Xu, Bin Xie, Yong Zhao, Nan Li, Xuetao Cao
Lysine methylation is an important posttranslational modification, implicated in various biological pathological conditions. The transcription factor interferon regulatory factor 3 (IRF3) is essential for antiviral innate immunity, yet the mechanism for methylation control of IRF3 activation remains unclear. In this paper, we discovered monomethylation of IRF3 at K366 is critical for IRF3 transcription activity in antiviral innate immunity. By mass spectrometry analysis of IRF3-associated proteins, we identified nuclear receptor-binding SET domain 3 (NSD3) as the lysine methyltransferase that directly binds to the IRF3 C-terminal region through its PWWP1 domain and methylates IRF3 at K366 via its SET domain...
November 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29098213/single-cell-analysis-of-early-antiviral-gene-expression-reveals-a-determinant-of-stochastic-ifnb1-expression
#11
Sultan Doğanay, Maurice Youzong Lee, Alina Baum, Jessie Peh, Sun-Young Hwang, Joo-Yeon Yoo, Paul J Hergenrother, Adolfo García-Sastre, Sua Myong, Taekjip Ha
RIG-I-like receptors (RLRs) are cytoplasmic sensors of viral RNA that trigger the signaling cascade that leads to type I interferon (IFN) production. Transcriptional induction of RLRs by IFN is believed to play the role of positive feedback to further amplify viral sensing. We found that RLRs and several other IFN-stimulated genes (ISGs) are induced early in viral infection independent of IFN. Expression of these early ISGs requires IRF3/IRF7 and is highly correlated amongst them. Simultaneous detection of mRNA of IFNB1, viral replicase, and ISGs revealed distinct populations of IFNB1 expressing and non-expressing cells which are highly correlated with the levels of early ISGs but are uncorrelated with IFN-dependent ISGs and viral gene expression...
November 13, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/29096690/tlr2-stimulation-impairs-anti-inflammatory-activity-of-m2-like-macrophages-generating-a-chimeric-m1-m2-phenotype
#12
Lilian Quero, Edveena Hanser, Tobias Manigold, André N Tiaden, Diego Kyburz
BACKGROUND: Toll-like receptors (TLRs) and macrophages play an important role in rheumatoid arthritis (RA). Currently, it is not clear whether inflammatory M1 or anti-inflammatory M2 predominate among the resident macrophages in the synovium. In the present study, we set out to investigate the impact of TLR stimulation on monocyte-derived M1 and M2 macrophage function and phenotype by mimicking the exposure to abundant TLR agonists as occurs in the context of RA. The response of macrophage subsets to TLR2 and TLR4 activation was evaluated on cluster of differentiation (CD) marker profile; cytokine secretion; gene expression; and NF-κB, interferon regulatory factors 3 and 7 (IRF3/7), and mitogen-activated protein kinase (MAPK) activation...
November 2, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29093090/inducible-microrna-3570-feedback-inhibits-the-rig-i-dependent-innate-immune-response-to-rhabdovirus-in-teleost-fish-by-targeting-mavs-ips-1
#13
Tianjun Xu, Qing Chu, Junxia Cui, Dekun Bi
Effectively recognizing invading viruses and subsequently inducing the innate antiviral immunity are essential for the host antiviral defense. Although these processes are closely regulated by the host to maintain the immune balance, viruses have evolved the abilities to downregulate or upregulate these processes for their survival. MicroRNAs (miRNAs) are a family of small non-coding RNAs that play vital roles in modulating host immune response. Accumulating evidence demonstrates that host miRNAs as mediators are involved in regulating viral replication and host anti-viral immunity in mammals...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29084253/pivotal-role-for-the-escrt-ii-complex-subunit-eap30-snf8-in-irf3-dependent-innate-antiviral-defense
#14
Kattareeya Kumthip, Darong Yang, Nan L Li, Yunzhi Zhang, Meiyun Fan, Aarti Sethuraman, Kui Li
The activation of interferon (IFN)-regulatory factor-3 (IRF3), characterized by phosphorylation and nuclear translocation of the latent transcription factor, is central to initiating innate antiviral responses. Whereas much has been learned about the upstream pathways and signaling mechanisms leading to IRF3 activation, how activated IRF3 operates in the nucleus to control transcription of IFNs remains obscure. Here we identify EAP30 (a.k.a, SNF8/VPS22), an endosomal sorting complex required for transport (ESCRT)-II subunit, as an essential factor controlling IRF3-dependent antiviral defense...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29080685/functional-characterization-of-interferon-regulatory-factor-5-and-its-role-in-the-innate-antiviral-immune-response
#15
Kete Ai, Kai Luo, Lihai Xia, Weihua Gao, Wei Hu, Zhitao Qi, Qiaoqing Xu
In mammals, type I interferons (IFNs) are primarily regulated by transcription factors of the IFN regulatory (IRF) family. Interferon regulatory factor 5 (IRF-5) plays pivotal roles in antiviral and inflammatory responses. In the present study, we found that zebrafish (Danio rerio) IRF5 is a key player in the regulation of the expression of type I IFN and its antiviral immune response. IRF5 was upregulated in zebrafish embryonic fibroblast cells (ZF4) when challenged with grass carp reovirus (GCRV). Moreover, the expression profiles of Mx, IFN, Viperin, and IRF7, but not IRF3, were upregulated by overexpression of IRF5 in Epithelioma papulosum cyprinid cells (EPCs)...
October 28, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29074580/an-interferon-independent-lncrna-promotes-viral-replication-by-modulating-cellular-metabolism
#16
Pin Wang, Junfang Xu, Yujia Wang, Xuetao Cao
Viruses regulate host metabolic networks to improve their survival. Hardly known are molecules responsive to viral infection that regulate such metabolic changes, which is essential for understanding viral infection. Here we identify a lncRNA induced by multiple viruses, but not by type I interferon (IFN-I), that facilitates viral replication in mouse and human cells. In vivo deficiency of lncRNA-ACOD1 significantly attenuates viral infection through IFN-I/IRF3-independent pathways. Cytoplasmic lncRNA-ACOD1 directly binds the metabolic enzyme glutamic-oxaloacetic transaminase (GOT2) near the substrate niche, enhancing its catalytic activity...
October 26, 2017: Science
https://www.readbyqxmd.com/read/29074428/identification-and-function-analysis-of-canine-stimulator-of-interferon-gene-sting
#17
Yuxiang Zhang, Mengyan Zhu, Gairu Li, Jie Liu, Xiaofeng Zhai, Ruyi Wang, Junyan Zhang, Gang Xing, Jinyan Gu, Liping Yan, Jing Lei, Haifeng Sun, Zhiyu Shi, Fei Liu, Boli Hu, Shuo Su, Jiyong Zhou
Stimulator of interferon gene (STING) plays an important role in the cyclic GMP-AMP synthase (cGAS)-mediated activation of type I IFN responses. In this study, we identified and cloned canine STING gene. Full-length STING encodes a 375 amino acid product that shares the highest similarity with feline STING. Highest levels of mRNA of canine STING were detected in the spleen and lungs while the lowest levels in the heart and muscle. Analysis of its cellular localization showed that STING is localizes to the endoplasmic reticulum...
October 24, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29074131/grouper-mavs-functions-as-a-crucial-antiviral-molecule-against-nervous-necrosis-virus-infection
#18
Youhua Huang, Jingcheng Zhang, Zhengliang Ouyang, Jiaxin Liu, Ya Zhang, Yin Hu, Xiaohong Huang, Qiwei Qin
Mitochondrial antiviral signaling protein (MAVS), also known as IPS-1, VISA, and Cardif, has been well studied for its crucial roles in the mammalian interferon immune response. To better understand the actions of MAVS in fish immune response, a MAVS homolog from orange spotted grouper (Epinephelus coioides) (EcMAVS) was cloned and characterized in this study. EcMAVS encoded a 563-amino acid peptide which showed 64% and 20% identity to rock bream (Oplegnathus fasciatus) and human (Homo sapiens), respectively...
October 23, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29070776/ccl5-is-induced-by-tlr-3-signaling-in-hucct1-human-biliary-epithelial-cells-possible-involvement-in-the-pathogenesis-of-biliary-atresia
#19
Taku Shimada, Tadaatsu Imaizumi, Kyogo Shirai, Tetsuya Tatsuta, Toshiro Kimura, Ryo Hayakari, Hidemi Yoshida, Tomoh Matsumiya, Hiroshi Kijima, Hiroki Mizukami, Kenichi Hakamada
Biliary atresia (BA) is a disease of the newborn that is characterized by progressive, inflammatory and sclerosing cholangiopathy. Innate immune responses to viral components are thought to be involved in the pathogenesis of BA. It is also reported that some chemokines, such as CCL5, are possibly involved in the pathogenesis of experimental animal model of BA. We treated human biliary epithelial HuCCT1 cells with polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA (dsRNA) which mimics viral RNA, and analyzed the CCL5 expression by quantitative reverse transcription-PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA)...
2017: Biomedical Research
https://www.readbyqxmd.com/read/29070073/the-dose-of-hbv-genome-contained-plasmid-has-a-great-impact-on-hbv-persistence-in-hydrodynamic-injection-mouse-model
#20
Lei Li, Sheng Li, Yun Zhou, Lu Yang, Di Zhou, Yan Yang, Mengji Lu, Dongliang Yang, Jingjiao Song
BACKGROUND: Hydrodynamic injection (HI) of hepatitis B virus (HBV) mouse model is an useful tool for HBV related research in vivo. However, only 40% of C57/BL6 mice injected with 10 μg HBV genome contained plasmid (pAAV-HBV1.2), serum HBsAg more than 6 months and none of the BALB/c mice injected with 10 μg pAAV-HBV1.2 plasmid DNA, serum HBsAg positive more than 4 weeks in the previous study. METHODS: In this study, C57/BL6 and BALB/c mice were hydrodynamic injected with different doses of pAAV-HBV1...
October 25, 2017: Virology Journal
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