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https://www.readbyqxmd.com/read/28516729/proteome-analysis-of-duck-tembusu-virus-dtmuv-infected-bhk-21-cells
#1
Xin Sun, Shengyu Wang, Xian Lin, Lianzhong Zhao, Dan Zhang, Chenyang Yi, Xiaomei Sun, Huanchun Chen, Meilin Jin
Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that has caused huge economic losses to the duck industry in China since 2010. Moreover, the infection has spread rapidly, posing a potential public health concern. In this study, iTRAQ approach was firstly used to quantitatively identify differentially expressed cellular proteins in DTMUV-infected BHK-21 cells which are usually employed to produce veterinary vaccines for DTMUV, as well as other flaviviruses by serial passage. We identified 192 differentially expressed cellular proteins, including 11 upregulated and 8 downregulated proteins at 24 h postinfection (hpi), as well as 25 upregulated and 151 downregulated proteins at 48 hpi, of which TLR9, DDX3X, and DDX5 may play important roles in virus propagation...
May 17, 2017: Proteomics
https://www.readbyqxmd.com/read/28505344/genetics-of-glaucoma
#2
Janey L Wiggs, Louis R Pasquale
Genetic and genomic studies, including genome-wide association studies (GWAS) have accelerated the discovery of genes contributing to glaucoma, the leading cause of irreversible blindness world-wide. Glaucoma can occur at all ages, with Mendelian inheritance typical for rare early onset disease (before age 40) and complex inheritance evident in common adult-onset forms of disease. Recent studies have suggested possible therapeutic targets for some patients with early-onset glaucoma based on the molecular and cellular events caused by MYOC, OPTN and TBK1 mutations...
May 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28493975/molecular-characterization-expression-of-chicken-tbk1-gene-and-its-effect-on-irf3-signaling-pathway
#3
Yan Wang, Yue Yin, Xi Lan, Fei Ye, Kai Tian, Xiaoling Zhao, Huadong Yin, Diyan Li, Hengyong Xu, Yiping Liu, Qing Zhu
TRAF family member-associated NF-κB activator (TANK)-binding kinase1 (TBK1) is a serine-threonine kinase at the crossroads of multiple interferon (IFN)-inducing signaling pathways in innate immunity. The importance of TBK1 in antiviral immunity is well established in mammal models, but in chicken, the molecular characterization and potential function of TBK1 remain unclear. In the present study, the open-reading frame (ORF) of chicken TBK1 (chTBK1) was cloned and characterized. The sequencing results revealed that the chTBK1 ORF consists of 2190 base pairs (bp) encoding a deduced protein of 729 amino acid residues...
2017: PloS One
https://www.readbyqxmd.com/read/28490595/sensing-of-hiv-1-entry-triggers-a-type-i-interferon-response-in-human-primary-macrophages
#4
Jérémie Decalf, Marion Desdouits, Vasco Rodrigues, François-Xavier Gobert, Matteo Gentili, Santy Marques-Ladeira, Célia Chamontin, Marylène Mougel, Bruna Cunha de Alencar, Philippe Benaroch
Along with CD4+ T lymphocytes, macrophages are a major cellular source of HIV-1 replication, and a potential viral reservoir. Following entry and reverse transcription in macrophages, cloaking of the viral cDNA by the HIV-1 capsid limits its cytosolic detection, enabling efficient replication. However, whether incoming HIV-1 particles are sensed by macrophages prior to reverse-transcription, remains unclear. Here, we show that HIV-1 triggers a broad expression of interferon-stimulated genes (ISG) in monocyte-derived macrophages within a few hours after infection...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28489052/crude-ecklonia-cava-flake-extracts-attenuate-inflammation-through-the-regulation-of-tlr4-signaling-pathway-in-lps-induced-raw264-7-cells
#5
Ji-Hyun Hwang, Kui-Jin Kim, Boo-Yong Lee
We investigated the beneficial effects of the crude Ecklonia cava flake (CEF), which is a residual product after polyphenol extraction from Ecklonia cava, on inflammation in LPS-stimulated RAW264.7 cells. A group of five different CEF extracts was obtained by a preparation process using water, hydrochloric acid or temperature. We observed that large-size (>19 kDa) CEF extract, which was extracted with water at 95 °C (CEF-W, 95 °C), suppressed the production of inflammatory cytokines by inhibiting its mRNA expression in LPS-induced RAW264...
May 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28487378/encephalomyocarditis-virus-3c-protease-attenuates-type-i-interferon-production-through-disrupting-tank-tbk1-ikk%C3%AE%C2%B5-irf3-complex
#6
Li Huang, Tao Xiong, Huibin Yu, Quan Zhang, Kunli Zhang, Changyao Li, Liang Hu, Yuanfeng Zhang, Lijie Zhang, Qinfang Liu, Shengnan Wang, Xijun He, Zhigao Bu, Xuehui Cai, Shangjin Cui, Jiangnan Li, Changjiang Weng
TRAF family member-associated NF-κB activator (TANK) is a scaffold protein that assembles into the interferon regulator factor 3 (IRF3)-phosphorylating TBK1-IKKε complex, where it is involved in regulating phosphorylation of the IRF3 and interferon (IFN) production. However, the functions of TANK in Encephalomyocarditis virus (EMCV) infection-induced type I IFN production are not fully understood. Here, we demonstrated that, instead of stimulating type I IFN production, the EMCV-HB10 strain infection potently inhibited Sendai virus (SeV)- and polyI:C-induced IRF3 phosphorylation and type I IFN production in HEK293T cells...
May 9, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28486191/nlrp4-is-an-essential-negative-regulator-of-fructose-induced-cardiac-injury-in-vitro-and-in-vivo
#7
Yong-Gang Lian, Hai-Ying Zhao, Sheng-Ji Wang, Qin-Liang Xu, Xiang-Jun Xia
High fructose consumption leads to metabolic syndrome and enhances cardiovascular disease risk. However, our knowledge of the molecular mechanism underlying the cardiac disease caused by fructose feeding is still poor. Nod-like receptors (NLRs) are intracellular sensors, responding to a variety of intracellular danger signals to induce injuries. NLRP4 is a negative regulator of nuclear factor-κB (NF-κB) signaling pathway through interactions with kinase IκB kinase (IKK). Here, we illustrated that NLRP4 attenuates pro-inflammatory cytokines releasing, including Transforming growth factor (TGF-β1), Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-18 (IL-18) and interleukin-6 (IL-6), in fructose-treated cardiac cells by means of RT-qPCR, and western blotting analysis...
May 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28484079/intrinsic-antiproliferative-activity-of-the-innate-sensor-sting-in-t-lymphocytes
#8
Silvia Cerboni, Nadia Jeremiah, Matteo Gentili, Ulf Gehrmann, Cécile Conrad, Marie-Claude Stolzenberg, Capucine Picard, Bénédicte Neven, Alain Fischer, Sébastian Amigorena, Frédéric Rieux-Laucat, Nicolas Manel
Activation of the cyclic dinucleotide sensor stimulator of interferon (IFN) genes (STING) is critical for IFN and inflammatory gene expression during innate immune responses. However, the role of STING in adaptive immunity is still unknown. In this study, we show that STING activation reduces the proliferation of T lymphocytes. This activity was independent of TBK1 and IRF3 recruitment and of type I IFN but required a distinct C-terminal domain of STING that activates NF-κB. Inhibition of cell proliferation by STING required its relocalization to the Golgi apparatus and caused mitotic errors...
May 8, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28459883/nlrx1-negatively-modulates-type-i-ifn-to-facilitate-kshv-reactivation-from-latency
#9
Zhe Ma, Sharon E Hopcraft, Fan Yang, Alex Petrucelli, Haitao Guo, Jenny P-Y Ting, Dirk P Dittmer, Blossom Damania
Kaposi's sarcoma-associated herpesvirus (KSHV) is a herpesvirus that is linked to Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). KSHV establishes persistent latent infection in the human host. KSHV undergoes periods of spontaneous reactivation where it can enter the lytic replication phase of its lifecycle. During KSHV reactivation, host innate immune responses are activated to restrict viral replication. Here, we report that NLRX1, a negative regulator of the type I interferon response, is important for optimal KSHV reactivation from latency...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28456633/optineurin-in-amyotrophic-lateral-sclerosis-multifunctional-adaptor-protein-at-the-crossroads-of-different-neuroprotective-mechanisms
#10
REVIEW
Andrea Markovinovic, Raffaello Cimbro, Tereza Ljutic, Jasna Kriz, Boris Rogelj, Ivana Munitic
When optineurin mutations showed up on the amyotrophic lateral sclerosis (ALS) landscape in 2010, they differed from most other ALS-causing genes. They seemed to act by loss- rather than gain-of-function, and it was unclear how a polyubiquitin-binding adaptor protein, which was proposed to regulate a variety of cellular functions including cell signaling and vesicle trafficking, could mediate neuroprotection. This review discusses the considerable progress that has been made since then. A large number of mutations in optineurin and optineurin-interacting proteins TANK-binding kinase (TBK1) and p62/SQSTM-1 have been found in the ALS patients, suggesting a common neuroprotective pathway...
April 26, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28455392/biomarker-accessible-and-chemically-addressable-mechanistic-subtypes-of-braf-melanoma
#11
Banu Eskiocak, Elizabeth McMillan, Saurabh Mendiratta, Rahul Kollipara, Hailei Zhang, Caroline Humphries, Changguang Wang, Jose Garcia-Rodriguez, Ming Ding, Aubhishek Zaman, Tracy Rosales, Ugur Eskiocak, Michael P Smith, Jessica Sudderth, Kakajan Komurov, Ralph J DeBerardinis, Claudia Wellbrock, Michael A Davies, Jennifer A Wargo, Yonghao Yu, Jef K De Brabander, Noelle S Williams, Lynda Chin, Helen Rizos, Georgina V Long, Ralf Kittler, Michael White
Genomic diversity among melanoma tumors limits durable control with conventional and targeted therapies. Nevertheless, pathological activation of the ERK1/2 pathway is a linchpin tumorigenic mechanism associated with the majority of primary and recurrent disease. Therefore, we sought to identify therapeutic targets that are selectively required for tumorigenicity in the presence of pathological ERK1/2 signaling. By integration of multi-genome chemical and genetic screens; recurrent architectural variants in melanoma tumor genomes; and patient outcome data; we identified 2 mechanistic subtypes of BRAF(V600) melanoma that inform new cancer cell biology and offer new therapeutic opportunities...
April 28, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28446676/grass-carp-reovirus-vp41-targets-fish-mita-to-abrogate-the-ifn-response
#12
Long-Feng Lu, Shun Li, Zhao-Xi Wang, Si-Qi Du, Dan-Dan Chen, Pin Nie, Yong-An Zhang
Although fish possess an efficient interferon (IFN) system to defend against aquatic virus infection, the grass carp reovirus (GCRV) still causes hemorrhagic disease in grass carp. To date, GCRV's strategy for evading the fish IFN response is still unknown. Here, we report that the GCRV VP41 inhibits fish IFN production by suppressing the phosphorylation of the mediator of IRF3 activation (MITA). First, the activation of the IFN promoter (IFNpro) stimulated by the mitochondrial antiviral signaling protein (MAVS) and MITA was decreased by the overexpression of VP41, whereas such activation induced by TANK-binding kinase 1 (TBK1) was not affected...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28428627/glucocorticoids-suppress-antimicrobial-autophagy-and-nitric-oxide-production-and-facilitate-mycobacterial-survival-in-macrophages
#13
Jinli Wang, Ruining Wang, Hui Wang, Xiaofan Yang, Jiahui Yang, Wenjing Xiong, Qian Wen, Li Ma
Chronic administration of glucocorticoids has been shown to render individuals highly susceptible to mycobacterial infection and lead to reactivation of latent bacilli. However, the effect of glucocorticoids on innate anti-mycobacterial defense, especially in macrophages remains largely unknown. Here, we found that glucocorticoids inhibited the innate immune response, antimicrobial nitric oxide production and autophagy in mycobacteria-challenged macrophages. Meanwhile, maturation and acidification of mycobacterial phagosomes were attenuated in RAW264...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28426911/tbk1-ikke-blockade-inhibits-mutant-sting-mediated-inflammatory-response-in-patient-cells
#14
Marie-Louise Frémond, Carolina Uggenti, Lien Van Eyck, Isabelle Melki, Vincent Bondet, Naoki Kitabayashi, Christina Hertel, Adrian Hayday, Bénédicte Neven, Yoann Rose, Darragh Duffy, Yanick J Crow, Mathieu P Rodero
OBJECTIVE: Gain-of-function mutations in TMEM173 encoding STING (stimulator of interferon genes) underlie a novel type I interferonopathy, minimally responsive to conventional immunosuppressive therapies and associated with high childhood morbidity and mortality. STING gain-of-function causes constitutive over secretion of interferon (IFN). We determined the effects of a TBK1/IKKE inhibitor (BX795) on IFN secretion and signaling in primary peripheral blood mononuclear cells (PBMCs) from four patients...
April 20, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28425986/p16ink4a-upregulation-mediated-by-tbk1-induces-retinal-ganglion-cell-senescence-in-ischemic-injury
#15
L U Li, Yin Zhao, Hong Zhang
Glaucoma is a leading cause of irreversible blindness worldwide that is characterized by progressive retinal ganglion cell (RGC) death. However, RGC senescence as a phase before RGC death, and the mechanism of RGC senescence remains unclear. Here, we demonstrate that TANK-binding protein 1 (TBK1) is upregulated in acute IOP elevation-induced ischemic retinas mouse model. Moreover, pre-treatment with the TBK1 inhibitor BX-795 reduced p16INK4a (p16) expression and RGC senescence. Upregulation of TBK1 via plasmid transfection increased Akt phosphorylation at Ser473 and Bmi1 phosphorylation...
April 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28423339/germ-cell-specific-inflammasome-component-nlrp14-negatively-regulates-cytosolic-nucleic-acid-sensing-to-promote-fertilization
#16
Takayuki Abe, Albert Lee, Ramaswami Sitharam, Jordan Kesner, Raul Rabadan, Sagi D Shapira
Cytosolic sensing of nucleic acids initiates tightly regulated programs to limit infection. Oocyte fertilization represents a scenario wherein inappropriate responses to exogenous yet non-pathogen-derived nucleic acids would have negative consequences. We hypothesized that germ cells express negative regulators of nucleic acid sensing (NAS) in steady state and applied an integrated data-mining and functional genomics approach to identify a rheostat of DNA and RNA sensing-the inflammasome component NLRP14. We demonstrated that NLRP14 interacted physically with the nucleic acid sensing pathway and targeted TBK1 (TANK binding kinase 1) for ubiquitination and degradation...
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28422568/cgas-sting-tbk1-irf3-7-induced-interferon-%C3%AE-contributes-to-the-clearing-of-non-tuberculous-mycobacterial-infection-in-mice
#17
Nanthapon Ruangkiattikul, Andreas Nerlich, Ketema Abdissa, Stefan Lienenklaus, Abdulhadi Suwandi, Nina Janze, Kristin Laarmann, Julia Spanier, Ulrich Kalinke, Siegfried Weiss, Ralph Goethe
Type I interferons (IFN-I), such as IFN-α and IFN-β are important messengers in the host response against bacterial infections. Knowledge about the role of IFN-I in infections by nontuberculous mycobacteria (NTM) is limited. Here we show that macrophages infected with pathogens of the Mycobacterium avium complex produced significantly lower amounts of IFN-β than macrophages infected with the opportunistic pathogen M. smegmatis. To dissect the molecular mechanisms of this phenomenon, we focused on the obligate pathogen Mycobacterium avium ssp paratuberculosis (MAP) and the opportunistic M...
April 19, 2017: Virulence
https://www.readbyqxmd.com/read/28415024/glucocorticoids-differentially-regulate-the-innate-immune-responses-of-tlr4-and-the-cytosolic-dna-sensing-pathway
#18
Jinli Wang, Ruining Wang, Jiahui Yang, Xiaofan Yang, Shengfeng Hu, Hui Wang, Chaoying Zhou, Wenjing Xiong, Qian Wen, Li Ma
Glucocorticoids (GCs) are widely used to treat the chronic inflammatory disorders because of their powerful anti-inflammatory properties; however, their effects on macrophage-mediated immune responses are not completely understood. In the present study, we found that GCs decreased LPS-mediated TBK1 activation and the expression of IFN-β, RANTES and CXCL-10; however, poly(dA:dT)-induced TBK1 activity and cytokine expression were not affected by GCs treatment. Furthermore, GCs decreased the expression of key autophagy-related genes (ATGs), including ATG5, ATG7 and ATG12, and inhibited autophagy in macrophages after LPS stimulation...
April 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28414768/gpatch3-negatively-regulates-rlr-mediated-innate-antiviral-responses-by-disrupting-the-assembly-of-visa-signalosome
#19
Ying Nie, Yong Ran, Hong-Yan Zhang, Zhe-Fu Huang, Zhao-Yi Pan, Su-Yun Wang, Yan-Yi Wang
Upon viral infection, retinoic acid-inducible gene I-like receptors (RLRs) recognize viral RNA and trigger a series of signaling events, leading to the induction of type I interferons (IFNs). These processes are delicately regulated to prevent excessive and harmful immune responses. In this study, we identified G patch domain-containing protein 3 (GPATCH3) as a negative regulator of RLR-mediated antiviral signaling pathways. Overexpression of GPATCH3 impaired RNA virus- triggered induction of downstream antiviral genes, whereas its knockdown had opposite effects and attenuated viral replication...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28412547/intracellular-dna-sensing-pathway-of-cgas-cgamp-is-decreased-in-human-newborns-and-young-children
#20
Zhan-Sheng Wang, Yu-Lu Liu, Nan Mi, Dao-Yun Duan
Newborns are highly susceptible to DNA virus infections, which may result from the characteristics of neonatal innate immune systems. Here we analyzed for the first time the development of innate immune sensing and signaling of intracellular DNA virus infection in human newborns and young children. Both mRNA and protein expression of cGAS, an intracellular DNA sensor, were shown to be significantly reduced in neonatal peripheral blood mononuclear cells (PBMCs). In addition, cGAS expression in neonatal PBMCs could be induced upon herpes simplex virus type 1 (HSV-1) or interferon-α (IFNα) stimulation...
April 13, 2017: Molecular Immunology
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