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https://www.readbyqxmd.com/read/28102839/foot-and-mouth-disease-virus-infection-suppresses-autophagy-and-nf-%C3%B0%C2%BAb-antiviral-responses-via-degradation-of-atg5-atg12-by-3c-pro
#1
Xuxu Fan, Shichong Han, Dan Yan, Yuan Gao, Yanquan Wei, Xiangtao Liu, Ying Liao, Huichen Guo, Shiqi Sun
Autophagy-related protein ATG5-ATG12 is an essential complex for the autophagophore elongation in autophagy, which has been reported to be involved in foot-and-mouth disease virus (FMDV) replication. Previous reports show that ATG5-ATG12 positively or negatively regulates type I interferon (IFN-α/β) pathway during virus infection. In this study, we found that FMDV infection rapidly induced LC3 lipidation and GFP-LC3 subcellular redistribution at the early infection stage in PK-15 cells. Along with infection time course to 2-5 h...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28100675/protein-synthesis-inhibition-and-gadd34-control-ifn-%C3%AE-heterogeneous-expression-in-response-to%C3%A2-dsrna
#2
Alexandre Dalet, Rafael J Argüello, Alexis Combes, Lionel Spinelli, Sebastien Jaeger, Mathieu Fallet, Thien-Phong Vu Manh, Andreia Mendes, Jessica Perego, Marisa Reverendo, Voahirana Camosseto, Marc Dalod, Tobias Weil, Manuel A Santos, Evelina Gatti, Philippe Pierre
In innate immune responses, induction of type-I interferons (IFNs) prevents virus spreading while viral replication is delayed by protein synthesis inhibition. We asked how cells perform these apparently contradictory activities. Using single fibroblast monitoring by flow cytometry and mathematical modeling, we demonstrate that type-I IFN production is linked to cell's ability to enter dsRNA-activated PKR-dependent translational arrest and then overcome this inhibition by decreasing eIF2α phosphorylation through phosphatase 1c cofactor GADD34 (Ppp1r15a) expression...
January 18, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28095500/senp7-potentiates-cgas-activation-by-relieving-sumo-mediated-inhibition-of-cytosolic-dna-sensing
#3
Ye Cui, Huansha Yu, Xin Zheng, Rui Peng, Qiang Wang, Yi Zhou, Rui Wang, Jiehua Wang, Bo Qu, Nan Shen, Qiang Guo, Xing Liu, Chen Wang
Cyclic GMP-AMP (cGAMP) synthase (cGAS, a.k.a. MB21D1), a cytosolic DNA sensor, catalyzes formation of the second messenger 2'3'-cGAMP that activates the stimulator of interferon genes (STING) signaling. How the cGAS activity is modulated remains largely unknown. Here, we demonstrate that sentrin/SUMO-specific protease 7 (SENP7) interacted with and potentiated cGAS activation. The small ubiquitin-like modifier (SUMO) was conjugated onto the lysine residues 335, 372 and 382 of cGAS, which suppressed its DNA-binding, oligomerization and nucleotidyl-transferase activities...
January 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28078587/organelle-separation-and-cell-signaling
#4
Leandro Silva Da Costa, Damien Arnoult
Recent findings indicate that some signaling hubs coalesce at the surfaces of organelles through the accumulation of ubiquitylated components required for the signal transduction. For instance, ubiquitylated components of the NF-κB pathway accumulated at the endoplasmic reticulum while ubiquitylated components of the IRF3 pathway are found at the Golgi apparatus. Here we describe simple methods to observe and assess these ubiquitylated components by immunoblotting using differential centrifugation and in vitro assays...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28077651/bromodomain-containing-4-brd4-couples-nf%C3%AE%C2%BAb-rela-with-airway-inflammation-and-the-irf-rig-i-amplification-loop-in-respiratory-syncytial-virus-infection
#5
Bing Tian, Jun Yang, Yingxin Zhao, Teodora Ivanciuc, Hong Sun, Roberto P Garofalo, Allan R Brasier
: The airway mucosa expresses protective interferon (IFN) and inflammatory cytokines in response to Respiratory Syncytial Virus (RSV) infection. In this study, we examine the role of bromodomain containing 4 (BRD4) in mediating this innate immune response in human small airway epithelial cells. We observe that RSV induces BRD4 to complex with NFκB/RelA. BRD4 is functionally required for expression of the NFκB-dependent inflammatory gene regulatory network (GRN), including the IFN Response Factor (IRFs)-1 and -7 that mediate a cross-talk pathway for RIG-I upregulation...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28069950/chronic-innate-immune-activation-of-tbk1-suppresses-mtorc1-activity-and-dysregulates-cellular-metabolism
#6
Maroof Hasan, Vijay K Gonugunta, Nicole Dobbs, Aktar Ali, Guillermo Palchik, Maria A Calvaruso, Ralph J DeBerardinis, Nan Yan
Three-prime repair exonuclease 1 knockout (Trex1(-/-)) mice suffer from systemic inflammation caused largely by chronic activation of the cyclic GMP-AMP synthase-stimulator of interferon genes-TANK-binding kinase-interferon regulatory factor 3 (cGAS-STING-TBK1-IRF3) signaling pathway. We showed previously that Trex1-deficient cells have reduced mammalian target of rapamycin complex 1 (mTORC1) activity, although the underlying mechanism is unclear. Here, we performed detailed metabolic analysis in Trex1(-/-) mice and cells that revealed both cellular and systemic metabolic defects, including reduced mitochondrial respiration and increased glycolysis, energy expenditure, and fat metabolism...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28062005/gga-mir-2127-downregulates-the-translation-of-chicken-p53-and-attenuates-chp53-mediated-innate-immune-response-against-ibdv-infection
#7
Wei Ouyang, Yong-Shan Wang, Kai Meng, Qun-Xing Pan, Xiao-Li Wang, Xing-Xia Xia, Yu-Mei Zhu, Zhen-Wei Bi, Hai-Bin Zhang, Kai Luo
Infectious bursal disease (IBD) is characterized by the immune suppression of infected birds. The molecular mechanism by which IBD virus (IBDV) suppresses the host immune system remains to be elucidated. The tumor suppressor protein p53 can inhibit the replication of various viruses, but its effect on IBDV remains unknown. This study established an in vitro infection model based on DF-1 cells (chicken embryo fibroblast cell line) to investigate the antiviral effects of chicken p53 (chp53) on IBDV infection...
January 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28056087/mita-sting-and-its-alternative-splicing-isoform-mrp-restrict-hepatitis-b-virus-replication
#8
Shuhui Liu, Kaitao Zhao, Xi Su, Lu Lu, He Zhao, Xianwen Zhang, Yun Wang, Chunchen Wu, Jizheng Chen, Yuan Zhou, Xue Hu, Yanyi Wang, Mengji Lu, Xinwen Chen, Rongjuan Pei
An efficient clearance of hepatitis B virus (HBV) requires the coordinated work of both the innate and adaptive immune responses. MITA/STING, an adapter protein of the innate immune signaling pathways, plays a key role in regulating innate and adaptive immune responses to DNA virus infection. Previously, we identified an alternatively spliced isoform of MITA/STING, called MITA-related protein (MRP), and found that MRP could specifically block MITA-mediated interferon (IFN) induction while retaining the ability to activate NF-κB...
2017: PloS One
https://www.readbyqxmd.com/read/28049762/the-tyrosine-kinase-src-promotes-phosphorylation-of-the-kinase-tbk1-to-facilitate-type-i-interferon-production-after-viral-infection
#9
Xuelian Li, Mingjin Yang, Zhou Yu, Songqing Tang, Lei Wang, Xuetao Cao, Taoyong Chen
Various pattern recognition receptors (PRRs) are activated in response to viral infection to stimulate the production of type I interferons (IFNs). However, central to the responses of all of these receptors is their activation of the kinase TBK1, which stimulates transcription by IFN regulatory factor 3 (IRF3). We investigated the mechanism by which the kinase activity of TBK1 is stimulated in response to viral infection. We found that the tyrosine kinase Src promoted the phosphorylation of TBK1 on Tyr(179) upon viral infection of RAW264...
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28045112/bromodomain-protein-brd3-promotes-ifnb1-transcription-via-enhancing-irf3-p300-complex-formation-and-recruitment-to-ifnb1-promoter-in-macrophages
#10
Wenhui Ren, Chunmei Wang, Qinlan Wang, Dezhi Zhao, Kai Zhao, Donghao Sun, Xingguang Liu, Chaofeng Han, Jin Hou, Xia Li, Qian Zhang, Xuetao Cao, Nan Li
As members of bromodomain and extra-terminal motif protein family, bromodomain-containing proteins regulate a wide range of biological processes including protein scaffolding, mitosis, cell cycle progression and transcriptional regulation. The function of these bromodomain proteins (Brds) in innate immune response has been reported but the role of Brd3 remains unclear. Here we find that virus infection significantly downregulate Brd3 expression in macrophages and Brd3 knockout inhibits virus-triggered IFN-β production...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28042704/development-of-an-in-vitro-immunobiotic-evaluation-system-against-rotavirus-infection-in-bovine-intestinal-epitheliocytes
#11
H Kobayashi, P Kanmani, T Ishizuka, A Miyazaki, J Soma, L Albarracin, Y Suda, T Nochi, H Aso, N Iwabuchi, J-Z Xiao, T Saito, J Villena, H Kitazawa
The bovine intestinal epithelial cell line (BIE cells) expresses the Toll-like receptor (TLR)3 and is able to mount an antiviral immune response after the stimulation with poly(I:C). In the present study, we aimed to further characterise the antiviral defence mechanisms in BIE cells by evaluating the innate immune response triggered by rotavirus (RV) infection. In addition, we attempted to determine whether immunobiotic bifidobacteria are able to confer protection of BIE cells against RV infection by beneficially modulating the antiviral immune response...
January 2, 2017: Beneficial Microbes
https://www.readbyqxmd.com/read/28041929/the-chlamydia-trachomatis-inclusion-membrane-protein-cpos-counteracts-sting-mediated-cellular-surveillance-and-suicide-programs
#12
Barbara S Sixt, Robert J Bastidas, Ryan Finethy, Ryan M Baxter, Victoria K Carpenter, Guido Kroemer, Jörn Coers, Raphael H Valdivia
Evading cell death is critical for Chlamydia to maintain a replicative niche, but the underlying mechanisms are unknown. We screened a library of Chlamydia mutants for modulators of cell death. Inactivation of the inclusion membrane protein CpoS (Chlamydia promoter of survival) induced rapid apoptotic and necrotic death in infected cells. The protection afforded by CpoS is limited to the inclusion in which it resides, indicating that it counteracts a spatially restricted pro-death signal. CpoS-deficient Chlamydia induced an exacerbated type I interferon response that required the host cGAS/STING/TBK1/IRF3 signaling pathway...
January 11, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28031478/trim65-catalized-ubiquitination-is-essential-for-mda5-mediated-antiviral-innate-immunity
#13
Xueting Lang, Tiantian Tang, Tengchuan Jin, Chen Ding, Rongbin Zhou, Wei Jiang
MDA5 plays a critical role in antiviral innate immunity by functioning as a cytoplasmic double-stranded RNA sensor that can activate type I interferon signaling pathways, but the mechanism for the activation of MDA5 is poorly understood. Here, we show that TRIM65 specifically interacts with MDA5 and promotes K63-linked ubiquitination of MDA5 at lysine 743, which is critical for MDA5 oligomerization and activation. Trim65 deficiency abolishes MDA5 agonist or encephalomyocarditis virus (EMCV)-induced interferon regulatory factor 3 (IRF3) activation and type I interferon production but has no effect on retinoic acid-inducible I (RIG-I), Toll-like receptor 3 (TLR3), or cyclic GMP-AMP synthase signaling pathways...
December 28, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28018864/mycobacterium-bovis-induces-endoplasmic-reticulum-stress-mediated-apoptosis-by-activating-irf3-in-a-murine-macrophage-cell-line
#14
Yongyong Cui, Deming Zhao, Srinand Sreevatsan, Chunfa Liu, Wei Yang, Zhiqi Song, Lifeng Yang, Paul Barrow, Xiangmei Zhou
Mycobacterium bovis (M. bovis) is highly adapted to macrophages and has developed multiple mechanisms to resist intracellular assaults. However, the host cells in turn deploy a multipronged defense mechanism to control bacterial infection. Endoplasmic reticulum (ER) stress-mediated apoptosis is one such primary defense mechanism. However, the role of interferon regulatory factor 3 (IRF3) between ER stress and apoptosis during M. bovis infection is unknown. Here, we demonstrate that M. bovis effectively induced apoptosis in murine macrophages...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28017736/comparative-and-temporal-transcriptome-analysis-of-peste-des-petits-ruminants-virus-infected-goat-peripheral-blood-mononuclear-cells
#15
Siddappa Manjunath, Bishnu Prasad Mishra, Bina Mishra, Aditya Prasad Sahoo, Ashok K Tiwari, Kaushal Kishore Rajak, D Muthuchelvan, Shikha Saxena, Lakshman Santra, Amit Ranjan Sahu, Sajad Ahmad Wani, R P Singh, Y P Singh, Aruna Pandey, Sonam Kanchan, R K Singh, Gandham Ravi Kumar, Sarath Chandra Janga
Peste des petits ruminanats virus (PPRV), a morbillivirus causes an acute, highly contagious disease - peste des petits ruminants (PPR), affecting goats and sheep. Sungri/96 vaccine strain is widely used for mass vaccination programs in India against PPR and is considered the most potent vaccine providing long-term immunity. However, occurrence of outbreaks due to emerging PPR viruses may be a challenge. In this study, the temporal dynamics of immune response in goat peripheral blood mononuclear cells (PBMCs) infected with Sungri/96 vaccine virus was investigated by transcriptome analysis...
February 2, 2017: Virus Research
https://www.readbyqxmd.com/read/28004841/the-citrus-flavonoid-naringenin-confers-protection-in-a-murine-endotoxaemia-model-through-ampk-atf3-dependent-negative-regulation-of-the-tlr4-signalling-pathway
#16
Xin Liu, Ning Wang, Shijun Fan, Xinchuan Zheng, Yongjun Yang, Yuanfeng Zhu, Yongling Lu, Qian Chen, Hong Zhou, Jiang Zheng
Excessive activation of the TLR4 signalling pathway is critical for inflammation-associated disorders, while negative regulators play key roles in restraining TLR4 from over-activation. Naringenin is a citrus flavonoid with remarkable anti-inflammatory activity, but the mechanisms underlying its inhibition of LPS/TLR4 signalling are less clear. This study investigated the molecular targets and therapeutic effects of naringenin in vitro and in vivo. In LPS-stimulated murine macrophages, naringenin suppressed the expression of TNF-α, IL-6, TLR4, inducible NO synthase (iNOS), cyclo-oxygenase-2 (COX2) and NADPH oxidase-2 (NOX2)...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27997564/nonstructural-protein-11-of-porcine-reproductive-and-respiratory-syndrome-virus-suppresses-both-mavs-and-rig-i-expression-as-one-of-the-mechanisms-to-antagonize-type-i-interferon-production
#17
Yan Sun, Hanzhong Ke, Mingyuan Han, Ning Chen, Weihuan Fang, Dongwan Yoo
Type I interferons (IFN-α/β) play a key role in antiviral defense, and porcine reproductive and respiratory syndrome virus (PRRSV) is known to down-regulate the IFN response in virus-infected cells and pigs. In this study, we showed that the overexpression of nsp11 of PRRSV induced a strong suppression of IFN production. Nsp11 suppressed both IRF3 and NF-κB activities when stimulated with a dsRNA analogue and TNF-α, respectively. This suppression was RLR dependent, since the transcripts and proteins of MAVS and RIG-I, two critical factors in RLR-mediated pathway, were both found to be reduced in the presence of overexpressed nsp11...
2016: PloS One
https://www.readbyqxmd.com/read/27992555/non-canonical-role-of-ikk%C3%AE-in-the-regulation-of-stat1-phosphorylation-in-antiviral-signaling
#18
Fei Xing, Tomoh Matsumiya, Yuko Shiba, Ryo Hayakari, Hidemi Yoshida, Tadaatsu Imaizumi
Non-self RNA is recognized by retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), inducing type I interferons (IFNs). Type I IFN promotes the expression of IFN-stimulated genes (ISGs), which requires the activation of signal transducer and activator of transcription-1 (STAT1). We previously reported that dsRNA induced STAT1 phosphorylation via a type I IFN-independent pathway in addition to the well-known type I IFN-dependent pathway. IκB kinase α (IKKα) is involved in antiviral signaling induced by dsRNA; however, its role is incompletely understood...
2016: PloS One
https://www.readbyqxmd.com/read/27983636/scoparone-inhibits-lps-simulated-inflammatory-response-by-suppressing-irf3-and-erk-in-bv-2-microglial-cells
#19
Duk-Yeon Cho, Hyun Myung Ko, Joonsoo Kim, Byung-Wook Kim, Yo-Sep Yun, Jeong-In Park, Palanivel Ganesan, Jin-Tae Lee, Dong-Kug Choi
Microglia activation and the release of various inflammatory cytokines are largely related to neurological diseases, including Parkinson's, Alzheimer's, and other brain diseases. The suppression of microglial cells using natural bioactive compounds has become increasingly important for brain therapy owing to the expected beneficial effect of lower toxicity. Scoparone (6,7-dimethoxycoumarin), a major bioactive compound found in various plant parts, including the inner shell of chestnut (Castanea crenata), was evaluated on lipopolysaccharide (LPS)-activated BV-2 microglia cells...
December 14, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27980081/ddx3-directly-regulates-traf3-ubiquitination-and-acts-as-a-scaffold-to-coordinate-assembly-of-signalling-complexes-downstream-of-mavs
#20
Lili Gu, Anthony Fullam, Niamh McCormack, Yvette Hoehn, Martina Schroeder
Human DEAD-box helicase 3 (DDX3) has been shown to contribute to type I interferon induction downstream of anti-viral pattern recognition receptors (PRRs). It binds to TANK-binding kinase 1 (TBK1) and IκB-kinase-ε (IKKε), the two key kinases mediating activation of Interferon regulatory factor (IRF) 3 and IRF7. We previously demonstrated that DDX3 facilitates IKKε activation downstream of RIG-I and then links the activated kinase to IRF3. In this study, we probed the interactions between DDX3 and other key signalling molecules in the RIG-I pathway and identified a novel direct interaction between DDX3 and TRAF3 mediated by a TRAF-interaction motif in the N-terminus of DDX3, which was required for TRAF3 ubiquitination...
December 15, 2016: Biochemical Journal
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