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https://www.readbyqxmd.com/read/28534493/usp13-negatively-regulates-antiviral-responses-by-deubiquitinating-sting
#1
He Sun, Qiang Zhang, Ying-Ying Jing, Man Zhang, Hai-Ying Wang, Zeng Cai, Tianzi Liuyu, Zhi-Dong Zhang, Tian-Chen Xiong, Yan Wu, Qi-Yun Zhu, Jing Yao, Hong-Bing Shu, Dandan Lin, Bo Zhong
STING (also known as MITA) is critical for host defence against viruses and the activity of STING is regulated by ubiquitination. However, the deubiquitination of STING is not fully understood. Here, we show that ubiquitin-specific protease 13 (USP13) is a STING-interacting protein that catalyses deubiquitination of STING. Knockdown or knockout of USP13 potentiates activation of IRF3 and NF-κB and expression of downstream genes after HSV-1 infection or transfection of DNA ligands. USP13 deficiency results in impaired replication of HSV-1...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28501626/a-method-for-the-detection-of-virus-infectivity-in-single-cells-and-real-time-towards-an-automated-fluorescence-neutralization-test
#2
Marylene Maistriau, Tea Carletti, Mohammad Khalid Zakaria, Luca Braga, Valentina Faoro, Vasileios Vasileiadis, Alessandro Marcello
Virus neutralizing antibodies are critical correlates of protection in vaccine development and are discriminatory in the plaque reduction neutralization test when used for the diagnosis of viral infections. However, neutralization assays are time consuming, labor intensive and highly variable, thus limiting their use. Advances in automated live imaging of cells opened new possibilities for standard virus diagnostic techniques such as neutralization assays. To this end, a reporter cell line based on the translocation of the transcription factor IRF3 in response to infection is proposed...
May 10, 2017: Virus Research
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/28489052/crude-ecklonia-cava-flake-extracts-attenuate-inflammation-through-the-regulation-of-tlr4-signaling-pathway-in-lps-induced-raw264-7-cells
#4
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
#5
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
#6
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/28485788/l6h21-prolonged-rats-survival-after-limb-allotransplantation-by-inhibiting-acute-rejection
#7
F-Z Yu, X Wen, W-L Ding, J-Y Zhu, S-H Du, Q-F Shen, X Ni, J Wang
OBJECTIVE: Preventing and reducing allograft rejection play a far more important role in limb allotransplantation. We previously found L6H21 could inhibit LPS-induced (lipopolysaccharide LPS) overexpression inflammatory factors in macrophages and specifically targets to MD-2 (myeloid differential protein-2 MD-2) required for TLR4 (Toll-like receptor 4 TLR4) activation and represented an important therapeutic target in inflammatory disorders. Therefore, we evaluated the effect and explored the mechanism of L6H21 in rats' limb allograft model...
April 2017: European Review for Medical and Pharmacological Sciences
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/28481329/yap-antagonizes-innate-antiviral-immunity-and-is-targeted-for-lysosomal-degradation-through-ikk%C3%A9-mediated-phosphorylation
#9
Shuai Wang, Feng Xie, Feng Chu, Zhengkui Zhang, Bing Yang, Tong Dai, Liang Gao, Lin Wang, Li Ling, Junling Jia, Hans van Dam, Jin Jin, Long Zhang, Fangfang Zhou
The transcription regulator YAP controls organ size by regulating cell growth, proliferation and apoptosis. However, whether YAP has a role in innate antiviral immunity is largely unknown. Here we found that YAP negatively regulated an antiviral immune response. YAP deficiency resulted in enhanced innate immunity, a diminished viral load, and morbidity in vivo. YAP blocked dimerization of the transcription factor IRF3 and impeded translocation of IRF3 to the nucleus after viral infection. Notably, virus-activated kinase IKKɛ phosphorylated YAP at Ser403 and thereby triggered degradation of YAP in lysosomes and, consequently, relief of YAP-mediated inhibition of the cellular antiviral response...
May 8, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28476672/gene-expression-profiles-associated-with-lymphocystis-disease-virus-lcdv-in-experimentally-infected-senegalese-sole-solea-senegalensis
#10
Carlos Carballo, Dolores Castro, Juan J Borrego, Manuel Manchado
In the present study, the pathogenesis of lymphocystis disease virus (LCDV) and the immune gene expression patterns associated with this viral infection were determined in the flatfish Senegalese sole. The results indicate that LCDV spreads rapidly from the peritoneal cavity through the bloodstream to reach target organs such as kidney, gut, liver, and skin/fin. The viral load was highest in kidney and reduced progressively thorough the experiment in spite of the viral major capsid protein gene was transcribed...
May 3, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28472924/identification-of-differentially-expressed-atlantic-salmon-mirnas-responding-to-salmonid-alphavirus-sav-infection
#11
Rune Andreassen, Nardos Tesfaye Woldemariam, Ine Østråt Egeland, Oleg Agafonov, Hilde Sindre, Bjørn Høyheim
BACKGROUND: MicroRNAs (miRNAs) control multiple biological processes including the innate immune responses by negative post-transcriptional regulation of gene expression. As there were no studies on the role(s) of miRNAs in viral diseases in Atlantic salmon, we aimed to identify miRNAs responding to salmonid alphavirus (SAV) infection. Their expression were studied at different time points post infection with SAV isolates associated with different mortalities. Furthermore, the genome sequences of the identified miRNAs were analysed to reveal putative cis-regulatory elements, and, finally, their putative target genes were predicted...
May 4, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28468885/rubicon-modulates-antiviral-type-i-ifn-signaling-by-targeting-irf3-dimerization
#12
Jae-Hoon Kim, Tae-Hwan Kim, Hyun-Cheol Lee, Chamilani Nikapitiya, Md Bashir Uddin, Min-Eun Park, Eun Seo Lee, Kiramage Chathuranga, Thilina U B Herath, W A Gayan Chathuranga, Jong-Soo Lee
Rubicon is a part of a Beclin-1-Vps34-containing autophagy complex. Rubicon induces antimicrobial responses upon TLR stimulation, and functions as a feedback inhibitor to prevent unbalanced proinflammatory responses depending on dectin-1 signaling. However, the role played by Rubicon during antiviral immune responses, particularly the type I interferon responses remains largely unknown. Here, we report that Rubicon acts as a negative regulator for virus-triggered IFN signaling. Knockdown of Rubicon promoted type I interferon signaling and inhibited virus replication, while overexpression of Rubicon has the opposite effect...
May 3, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28467369/developmental-control-of-nramp1-slc11a1-expression-in-professional-phagocytes
#13
Mathieu F M Cellier
NRAMP1 (SLC11A1) is a professional phagocyte membrane importer of divalent metals that contributes to iron recycling at homeostasis and to nutritional immunity against infection. Analyses of data generated by several consortia and additional studies were integrated to hypothesize mechanisms restricting NRAMP1 expression to mature phagocytes. Results from various epigenetic and transcriptomic approaches were collected for mesodermal and hematopoietic cell types and compiled for combined analysis with results of genetic studies associating single nucleotide polymorphisms (SNPs) with variations in NRAMP1 expression (eQTLs)...
May 3, 2017: Biology
https://www.readbyqxmd.com/read/28465426/a-novel-agonist-of-the-trif-pathway-induces-a-cellular-state-refractory-to-replication-of-zika-chikungunya-and-dengue-viruses
#14
Kara M Pryke, Jinu Abraham, Tina M Sali, Bryan J Gall, Iris Archer, Andrew Liu, Shelly Bambina, Jason Baird, Michael Gough, Marita Chakhtoura, Elias K Haddad, Ilsa T Kirby, Aaron Nilsen, Daniel N Streblow, Alec J Hirsch, Jessica L Smith, Victor R DeFilippis
The ongoing concurrent outbreaks of Zika, Chikungunya, and dengue viruses in Latin America and the Caribbean highlight the need for development of broad-spectrum antiviral treatments. The type I interferon (IFN) system has evolved in vertebrates to generate tissue responses that actively block replication of multiple known and potentially zoonotic viruses. As such, its control and activation through pharmacological agents may represent a novel therapeutic strategy for simultaneously impairing growth of multiple virus types and rendering host populations resistant to virus spread...
May 2, 2017: MBio
https://www.readbyqxmd.com/read/28465253/anti-inflammatory-action-of-2-carbomethoxy-2-3-epoxy-3-prenyl-1-4-naphthoquinone-cmep-nq-suppresses-both-the-myd88-dependent-and-trif-dependent-pathways-of-tlr4-signaling-in-lps-stimulated-raw264-7-cells
#15
Hyun Ju Woo, Do Youn Jun, Ji Young Lee, Hae Sun Park, Mi Hee Woo, Sook Jahr Park, Sang Chan Kim, Chae Ha Yang, Young Ho Kim
ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Rubia cordifolia L. have been widely used as a traditional herbal medicine in Northeast Asia for treatment of inflammatory diseases. AIM OF THE STUDY: To elucidate the anti-inflammatory mechanism of 2-carbomethoxy-2,3-epoxy-3- prenyl-1,4-naphthoquinone (CMEP-NQ), purified from the roots of R. cordifolia L. as the major anti-inflammatory component, in LPS-treated RAW264.7 murine macrophage cells. MATERIALS AND METHODS: Anti-inflammatory activity of CMEP-NQ was investigated in LPS-treated RAW264...
April 29, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28464285/elimination-of-gpr146-mediated-antiviral-function-through-irf3-hes1-signaling-pathway
#16
Hongjun Huang, Na Zhang, Qingqing Xiong, Ruoyu Chen, Chengfei Zhang, Ning Wang, Li Wang, Hua Ren, Mingyao Liu, Min Qian, Bing Du
As the most important host defense against viral infection, interferon (IFN) stimulates hundreds of antiviral genes (ISGs) that together establish an "antiviral state". However, the antiviral function of most ISGs in viral infection still need further exploration. Here, we demonstrated that the expression of G-protein-coupled receptor 146 (GPR146) is highly increased by both IFN-β and IFN-γ in a STAT1-dependent signaling pathway. Most importantly, overexpression of GPR146 protects the host cells from Vesicular stomatitis virus and Newcastle disease virus infection but not Herpes simplex virus...
May 2, 2017: Immunology
https://www.readbyqxmd.com/read/28448848/transmissible-gastroenteritis-virus-infection-induces-nf-%C3%AE%C2%BAb-activation-through-rlr-mediated-signaling
#17
Zhen Ding, Kang An, Lilan Xie, Wei Wu, Ruoxi Zhang, Dang Wang, Ying Fang, Huanchun Chen, Shaobo Xiao, Liurong Fang
Transmissible gastroenteritis virus (TGEV) is a porcine enteric coronavirus which causes lethal severe watery diarrhea in piglets. The pathogenesis of TGEV is strongly associated with inflammation. In this study, we found that TGEV infection activates transcription factors NF-κB, IRF3 and AP-1 in a time- and dose-dependent manner in porcine kidney cells. Treatment with the NF-κB-specific inhibitor BAY11-7082 significantly decreased TGEV-induced proinflammatory cytokine production, but did not affect virus replication...
April 24, 2017: Virology
https://www.readbyqxmd.com/read/28446676/grass-carp-reovirus-vp41-targets-fish-mita-to-abrogate-the-ifn-response
#18
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/28435159/ifitm3-inhibits-virus-triggered-induction-of-type-i-interferon-by-mediating-autophagosome-dependent-degradation-of-irf3
#19
Li-Qun Jiang, Tian Xia, Yun-Hong Hu, Ming-Shun Sun, Shuang Yan, Cao-Qi Lei, Hong-Bing Shu, Ji-Hua Guo, Yu Liu
Interferon-induced transmembrane protein 3 (IFITM3) is a restriction factor that can be induced by viral infection and interferons (IFNs). It inhibits the entry and replication of many viruses, which are independent of receptor usage but dependent on processes that occur in endosomes. In this study, we demonstrate that IFITM3 plays important roles in regulating the RNA-virus-triggered production of IFN-β in a negative-feedback manner. Overexpression of IFITM3 inhibited Sendai virus-triggered induction of IFN-β, whereas knockdown of IFITM3 had the opposite effect...
April 24, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28435158/a-balancing-act-between-ifitm3-and-irf3
#20
Temet M McMichael, Mahesh Chemudupati, Jacob S Yount
No abstract text is available yet for this article.
April 24, 2017: Cellular & Molecular Immunology
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