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https://www.readbyqxmd.com/read/27902332/inhibition-of-hepatitis-b-virus-replication-by-activation-of-the-cgas-sting-pathway
#1
Jing He, Ruidong Hao, Dan Liu, Xing Liu, Shaoshuai Wu, Shuting Guo, Yuan Wang, Deyin Guo
Cyclic GMP-AMP (cGAMP) synthase (cGAS) senses cytosolic DNA and catalyzes synthesis of the second messenger cGAMP, which activates the downstream signaling adaptor protein STING, leading to the expression of type I interferons. Hepatitis B virus (HBV) is a small DNA virus, and the cGAS-STING pathway may inhibit HBV RNA synthesis and viral assembly in cell culture, but the exact roles of cGAS pathway in the restriction of HBV replication in infection systems remain to be elucidated. In this study, we showed that the replication of HBV was significantly inhibited both in cell culture and in vivo in a mouse model when the cGAS-STING pathway was activated by dsDNA or cGAMP...
October 31, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27889408/an-rna-based-fluorescent-biosensor-for-high-throughput-analysis-of-the-cgas-cgamp-sting-pathway
#2
Debojit Bose, Yichi Su, Assaf Marcus, David H Raulet, Ming C Hammond
In mammalian cells, the second messenger (2'-5',3'-5') cyclic guanosine monophosphate-adenosine monophosphate (2',3'-cGAMP), is produced by the cytosolic DNA sensor cGAMP synthase (cGAS), and subsequently bound by the stimulator of interferon genes (STING) to trigger interferon response. Thus, the cGAS-cGAMP-STING pathway plays a critical role in pathogen detection, as well as pathophysiological conditions including cancer and autoimmune disorders. However, studying and targeting this immune signaling pathway has been challenging due to the absence of tools for high-throughput analysis...
November 18, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/27863906/post-translational-control-of-intracellular-pathogen-sensing-pathways
#3
REVIEW
Cindy Chiang, Michaela U Gack
Mammalian cells recognize virus-derived nucleic acids using a defined set of intracellular sensors including the DNA sensors cyclic GMP-AMP (cGAMP) synthase (cGAS) and interferon gamma (IFNγ)-inducible protein 16 (IFI16) as well as viral RNA receptors of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family. Following innate immune recognition, these sensors launch an immune response that is characterized by the transcriptional upregulation of many antiviral molecules, including proinflammatory cytokines, chemokines, and IFN-stimulated genes...
November 15, 2016: Trends in Immunology
https://www.readbyqxmd.com/read/27863149/cgas-expression-in-patients-with-systemic-lupus-erythematosus
#4
Jie An, Laura Durcan, Reynold M Karr, Tracy A Briggs, Gillian I Rice, Thomas H Teal, Joshua J Woodward, Keith B Elkon
OBJECTIVES Type I interferon (IFN-I) is implicated in the pathogenesis of Systemic Lupus Erythematosus (SLE) and 'interferonopathies' such as Aicardi-Goutieres Syndrome. A recently discovered DNA-activated IFN-I pathway, cyclic GMP-AMP (cGAMP) synthase (cGAS) is linked to AGS and mouse models of lupus. The aim of this study was to determine whether the cGAS pathway contributes to IFN-I production in SLE patients. METHODS SLE disease activity was measured by SELENA-SLEDAI. cGAS and interferon stimulated gene (ISG) mRNA expression was quantified by quantitative PCR ...
November 18, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27830700/sensing-of-hsv-1-by-the-cgas-sting-pathway-in-microglia-orchestrates-antiviral-defence-in-the-cns
#5
Line S Reinert, Katarína Lopušná, Henriette Winther, Chenglong Sun, Martin K Thomsen, Ramya Nandakumar, Trine H Mogensen, Morten Meyer, Christian Vægter, Jens R Nyengaard, Katherine A Fitzgerald, Søren R Paludan
Herpes simplex encephalitis (HSE) is the most common form of acute viral encephalitis in industrialized countries. Type I interferon (IFN) is important for control of herpes simplex virus (HSV-1) in the central nervous system (CNS). Here we show that microglia are the main source of HSV-induced type I IFN expression in CNS cells and these cytokines are induced in a cGAS-STING-dependent manner. Consistently, mice defective in cGAS or STING are highly susceptible to acute HSE. Although STING is redundant for cell-autonomous antiviral resistance in astrocytes and neurons, viral replication is strongly increased in neurons in STING-deficient mice...
November 10, 2016: Nature Communications
https://www.readbyqxmd.com/read/27828887/comprehensive-geriatric-assessment-for-trauma-operationalizing-the-trauma-quality-improvement-program-directive
#6
Stephanie Devore, Sara E Parli, Douglas R Oyler, Andrew Bernard
Elderly patients are the fastest growing trauma demographic and present some of the most complicated clinical challenges. This feasibility study employed observational data from a geriatric cohort. Comprehensive geriatric assessments (CGAs) were performed biweekly on eligible patients, 65 years or older, who met screening criteria. Mobility, activities of daily living impairment, frailty, and depression were screened and documented, and along with summative recommendations, were entered into the medical record, communicated to the patient's primary care provider, and discussed with family...
November 2016: Journal of Trauma Nursing: the Official Journal of the Society of Trauma Nurses
https://www.readbyqxmd.com/read/27824940/invertebrate-iridescent-virus-6-a-dna-virus-stimulates-a-mammalian-innate-immune-response-through-rig-i-like-receptors
#7
Laura R H Ahlers, Reginaldo G Bastos, Aoi Hiroyasu, Alan G Goodman
Insects are not only major vectors of mammalian viruses, but are also host to insect-restricted viruses that can potentially be transmitted to mammals. While mammalian innate immune responses to arboviruses are well studied, less is known about how mammalian cells respond to viruses that are restricted to infect only invertebrates. Here we demonstrate that IIV-6, a DNA virus of the family Iridoviridae, is able to induce a type I interferon-dependent antiviral immune response in mammalian cells. Although IIV-6 is a DNA virus, we demonstrate that the immune response activated during IIV-6 infection is mediated by the RIG-I-like receptor (RLR) pathway, and not the canonical DNA sensing pathway via cGAS/STING...
2016: PloS One
https://www.readbyqxmd.com/read/27813878/antimalarial-drugs-as-immune-modulators-new-mechanisms-for-old-drugs
#8
Jie An, Mark Minie, Tomikazu Sasaki, Joshua J Woodward, Keith B Elkon
The best known of the naturally occurring antimalarial compounds are quinine, extracted from cinchona bark, and artemisinin (qinghao), extracted from Artemisia annua in China. These and other derivatives are now chemically synthesized and remain the mainstay of therapy to treat malaria. The beneficial effects of several of the antimalarial drugs (AMDs) on clinical features of autoimmune disorders were discovered by chance during WorldWar II. In this review, we discuss the chemistry of AMDs and their mechanisms of action, emphasizing how they may impact multiple pathways of innate immunity...
October 21, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27801797/electrochemical-behavior-and-determination-of-chlorogenic-acid-based-on-multi-walled-carbon-nanotubes-modified-screen-printed-electrode
#9
Xiaoyan Ma, Hongqiao Yang, Huabin Xiong, Xiaofen Li, Jinting Gao, Yuntao Gao
In this paper, the multi-walled carbon nanotubes modified screen-printed electrode (MWCNTs/SPE) was prepared and the MWCNTs/SPE was employed for the electrochemical determination of the antioxidant substance chlorogenic acids (CGAs). A pair of well-defined redox peaks of CGA was observed at the MWCNTs/SPE in 0.10 mol/L acetic acid-sodium acetate buffer (pH 6.2) and the electrode process was adsorption-controlled. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) methods for the determination of CGA were proposed based on the MWCNTs/SPE...
October 27, 2016: Sensors
https://www.readbyqxmd.com/read/27793594/cross-regulation-of-two-type-i-interferon-signaling-pathways-in-plasmacytoid-dendritic-cells-controls-anti-malaria-immunity-and-host-mortality
#10
Xiao Yu, Baowei Cai, Mingjun Wang, Peng Tan, Xilai Ding, Jian Wu, Jian Li, Qingtian Li, Pinghua Liu, Changsheng Xing, Helen Y Wang, Xin-Zhuan Su, Rong-Fu Wang
Type I interferon (IFN) is critical for controlling pathogen infection; however, its regulatory mechanisms in plasmacytoid cells (pDCs) still remain unclear. Here, we have shown that nucleic acid sensors cGAS-, STING-, MDA5-, MAVS-, or transcription factor IRF3-deficient mice produced high amounts of type I IFN-α and IFN-β (IFN-α/β) in the serum and were resistant to lethal plasmodium yoelii YM infection. Robust IFN-α/β production was abolished when gene encoding nucleic acid sensor TLR7, signaling adaptor MyD88, or transcription factor IRF7 was ablated or pDCs were depleted...
November 15, 2016: Immunity
https://www.readbyqxmd.com/read/27790334/comparison-between-the-efficacies-of-risperidone-with-haloperidol-in-the-treatment-of-attention-deficit-hyperactivity-disorder-adhd-among-preschoolers-a-randomized-double-blind-clinical-trial
#11
Forough Riahi, Ashraf Tashakori, Leila Abdi
BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric disease with a worldwide pooled prevalence of 5.29%. OBJECTIVE: To compare the efficacy of Risperidone with Haloperidol in the treatment of attention-deficit hyperactivity disorder (ADHD) among 3- to 6-year-old children. METHODS: In a 6-week double-blind clinical trial, the efficacy of Risperidone 0.5-2 mg with a dose of maximum Haloperidol 0.075 mg/kg was assessed in 39 children aged 3-6 years...
September 2016: Electronic Physician
https://www.readbyqxmd.com/read/27764250/histone-h2b-ifi16-recognition-of-nuclear-herpesviral-genome-induces-cytoplasmic-interferon-%C3%AE-responses
#12
Jawed Iqbal, Mairaj Ahmed Ansari, Binod Kumar, Dipanjan Dutta, Arunava Roy, Leela Chikoti, Gina Pisano, Sujoy Dutta, Shahrooz Vahedi, Mohanan Valiya Veettil, Bala Chandran
IFI16 (gamma-interferon-inducible protein 16), a predominantly nuclear protein involved in transcriptional regulation, also functions as an innate immune response DNA sensor and induces the IL-1β and antiviral type-1 interferon-β (IFN-β) cytokines. We have shown that IFI16, in association with BRCA1, functions as a sequence independent nuclear sensor of episomal dsDNA genomes of KSHV, EBV and HSV-1. Recognition of these herpesvirus genomes resulted in IFI16 acetylation, BRCA1-IFI16-ASC-procaspase-1 inflammasome formation, cytoplasmic translocation, and IL-1β generation...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27751656/molecular-requirements-for-sensing-of-intracellular-microbial-nucleic-acids-by-the-innate-immune-system
#13
Stefanie Luecke, Søren R Paludan
Nucleic acids sensors of the innate immune system recognize various RNA and DNA structures during infection to induce transcription of interferon and pro-inflammatory cytokines and activation of inflammasomes. Cytosolic RNA is recognized by RIG-I and MDA5, while intracellular DNA is sensed among others by cGAS, AIM2, IFI16 and RNA polymerase III. The diversity of nucleic acid species produced during infection in the cytosol and nucleus and the limited chemical differences between self and non-self nucleic acids challenge the host's innate pattern recognition system to ensure reliable sensing while avoiding immune activation by self nucleic acids...
October 14, 2016: Cytokine
https://www.readbyqxmd.com/read/27736643/cgas-mediated-innate-immunity-spreads-intercellularly-through-hiv-1-env-induced-membrane-fusion-sites
#14
Shuting Xu, Aurélie Ducroux, Aparna Ponnurangam, Gabrielle Vieyres, Sergej Franz, Mathias Müsken, Thomas Zillinger, Angelina Malassa, Ellen Ewald, Veit Hornung, Winfried Barchet, Susanne Häussler, Thomas Pietschmann, Christine Goffinet
Upon sensing cytoplasmic retroviral DNA in infected cells, cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the cyclic dinucleotide cGAMP, which activates STING to trigger a type I interferon (IFN) response. We find that membrane fusion-inducing contact between donor cells expressing the HIV envelope (Env) and primary macrophages endogenously expressing the HIV receptor CD4 and coreceptor enable intercellular transfer of cGAMP. This cGAMP exchange results in STING-dependent antiviral IFN responses in target macrophages and protection from HIV infection...
October 12, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27733862/stimulatory-effects-of-acibenzolar-s-methyl-on-chlorogenic-acids-biosynthesis-in-centella-asiatica-cells
#15
Efficient N Ncube, Paul A Steenkamp, Ntakadzeni E Madala, Ian A Dubery
Centella asiatica is a perrenial herb that grows in tropical regions with numerous medicinal properties mostly attributed to the presence of pentacyclic triterpenoids. Interestingly, this plant also possess a significant amount of phenylpropanoid-derived chlorogenic acids (CGAs) that have recently been reported to confer neuroprotective properties. In a biotechnological attempt to increase the biosynthesis of CGA-derivatives in cultured Centella cells, acibenzolar-S-methyl was applied as a xenobiotic inducer in combination with quinic acid and shikimic acid as precursor molecules...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27719962/selective-enzymatic-hydrolysis-of-chlorogenic-acid-lactones-in-a-model-system-and-in-a-coffee-extract-application-to-reduction-of-coffee-bitterness
#16
Karin Kraehenbuehl, Nicole Page-Zoerkler, Olivier Mauroux, Karin Gartenmann, Imre Blank, Rachid Bel-Rhlid
Chlorogenic acid lactones have been identified as key contributors to coffee bitterness. These compounds are formed during roasting by dehydration and cyclization of their precursors, the chlorogenic acids (CGAs). In the present study, we investigated an approach to decompose these lactones in a selective way without affecting the positive coffee attributes developed during roasting. A model system composed of (3-caffeoylquinic acid lactone (3-CQAL), 4- caffeoyl quinic acid lactone (4-CQAL), and 4-feruloylquinic acid lactone (4-FQAL)) was used for the screening of enzymes before treatment of the coffee extracts...
March 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/27707838/activation-of-sting-dependent-innate-immune-signaling-by-s-phase-specific-dna-damage-in-breast-cancer
#17
Eileen E Parkes, Steven M Walker, Laura E Taggart, Nuala McCabe, Laura A Knight, Richard Wilkinson, Karen D McCloskey, Niamh E Buckley, Kienan I Savage, Manuel Salto-Tellez, Stephen McQuaid, Mary T Harte, Paul B Mullan, D Paul Harkin, Richard D Kennedy
BACKGROUND: Previously we identified a DNA damage response-deficient (DDRD) molecular subtype within breast cancer. A 44-gene assay identifying this subtype was validated as predicting benefit from DNA-damaging chemotherapy. This subtype was defined by interferon signaling. In this study, we address the mechanism of this immune response and its possible clinical significance. METHODS: We used immunohistochemistry (IHC) to characterize immune infiltration in 184 breast cancer samples, of which 65 were within the DDRD subtype...
January 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/27706894/cgas-cgamp-sting-the-three-musketeers-of-cytosolic-dna-sensing-and-signaling
#18
Jianli Tao, Xiang Zhou, Zhengfan Jiang
Innate immunity is the first line of host defense against invading pathogens. The detection of aberrant nucleic acids which represent some conserved PAMPs triggers robust type I IFN-mediated innate immune responses. Host- or pathogen-derived cytosolic DNA binds and activates the DNA sensor cGAS, which synthesizes the second messenger 2'3'-cGAMP and triggers STING-dependent downstream signaling. Here, we highlight recent progress in cGAS-cGAMP-STING, the Three Musketeers of cytosolic DNA sensing and signaling, and their essential roles in infection, autoimmune diseases, and cancer...
October 5, 2016: IUBMB Life
https://www.readbyqxmd.com/read/27705945/interaction-between-susceptibility-loci-in-cgas-sting-pathway-mhc-gene-and-hpv-infection-on-the-risk-of-cervical-precancerous-lesions-in-chinese-population
#19
Di Xiao, Weihuang Huang, Meiling Ou, Congcong Guo, Xingguang Ye, Yang Liu, Man Wang, Baohuan Zhang, Na Zhang, Shiqi Huang, Jiankun Zang, Zixing Zhou, Zihao Wen, Chengli Zeng, Chenfei Wu, Chuican Huang, Xiangcai Wei, Guang Yang, Chunxia Jing
Human papillomavirus (HPV) infection is a definite risk factor for cervical cancer. Nevertheless, only some infected individuals actually develop cervical cancer. The cGAS-STING pathway in innate immunity plays an important role in protecting against HPV infection. Chen et al. described that the rs2516448 SNP in the MHC locus may affect susceptibility to cervical cancer, a finding that we attempted to replicate in a Chinese population. To investigate the effects of cGAS, STING and MHC polymorphisms on susceptibility to cervical precancerous lesions, 9 SNPs were analyzed in 164 cervical precancerous lesion cases and 428 controls...
October 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27705790/hiv-triggers-a-cgas-dependent-vpu-and-vpr-regulated-type-i-interferon-response-in-cd4-t-cells
#20
Jolien Vermeire, Ferdinand Roesch, Daniel Sauter, Réjane Rua, Dominik Hotter, Anouk Van Nuffel, Hanne Vanderstraeten, Evelien Naessens, Veronica Iannucci, Alessia Landi, Wojciech Witkowski, Ann Baeyens, Frank Kirchhoff, Bruno Verhasselt
Several pattern-recognition receptors sense HIV-1 replication products and induce type I interferon (IFN-I) production under specific experimental conditions. However, it is thought that viral sensing and IFN induction are virtually absent in the main target cells of HIV-1 in vivo. Here, we show that activated CD4(+) T cells sense HIV-1 infection through the cytosolic DNA sensor cGAS and mount a bioactive IFN-I response. Efficient induction of IFN-I by HIV-1 infection requires proviral integration and is regulated by newly expressed viral accessory proteins: Vpr potentiates, while Vpu suppresses cGAS-dependent IFN-I induction...
October 4, 2016: Cell Reports
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