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Stimulator of interferon genes

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https://www.readbyqxmd.com/read/28223347/intact-pneumococci-trigger-transcription-of-interferon-related-genes-in-human-monocytes-while-fragmented-autolyzed-bacteria-subvert-this-response
#1
Susann Skovbjerg, Rickard Nordén, Anna Martner, Ebba Samuelsson, Lars Hynsjö, Agnes E Wold
A peculiar trait of pneumococci (Streptococcus pneumoniae) is their propensity to undergo spontaneous lysis during stationary growth due to activation of the enzyme autolysin (LytA) that fragments the peptidoglycan cell wall. The fragments that are generated upon autolysis impair phagocytosis and reduce production of IL-12 and IFN-γ by human leukocytes in response to intact pneumococci, thereby impeding crucial host defenses. The objective was to identify additional monocyte genes whose transcription is induced by intact pneumococci, and subverted by autolyzed bacteria...
February 21, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28222744/herpes-simplex-virus-1-infection-dampens-the-immediate-early-antiviral-innate-immunity-signaling-from-peroxisomes-by-tegument-protein-vp16
#2
Chunfu Zheng, Chenhe Su
BACKGROUND: Herpes simplex virus 1 (HSV-1) is an archetypal member of the alphaherpesvirus subfamily with a large genome encoding over 80 proteins, many of which play a critical role in virus-host interactions and immune modulation. Upon viral infections, the host cells activate innate immune responses to restrict their replications. Peroxisomes, which have long been defined to regulate metabolic activities, are reported to be important signaling platforms for antiviral innate immunity...
February 21, 2017: Virology Journal
https://www.readbyqxmd.com/read/28219022/rationale-for-stimulator-of-interferon-genes-targeted-cancer-immunotherapy
#3
REVIEW
Thaiz Rivera Vargas, Isis Benoit-Lizon, Lionel Apetoh
The efficacy of checkpoint inhibitor therapy illustrates that cancer immunotherapy, which aims to foster the host immune response against cancer to achieve durable anticancer responses, can be successfully implemented in a routine clinical practice. However, a substantial proportion of patients does not benefit from this treatment, underscoring the need to identify alternative strategies to defeat cancer. Despite the demonstration in the 1990's that the detection of danger signals, including the nucleic acids DNA and RNA, by dendritic cells (DCs) in a cancer setting is essential for eliciting host defence, the molecular sensors responsible for recognising these danger signals and eliciting anticancer immune responses remain incompletely characterised, possibly explaining the disappointing results obtained so far upon the clinical implementation of DC-based cancer vaccines...
February 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28219017/interaction-between-fmdv-l-pro-and-transcription-factor-adnp-is-required-for-optimal-viral-replication
#4
Gisselle N Medina, Giselle M Knudsen, Alexander L Greninger, Anna Kloc, Fayna Díaz-San Segundo, Elizabeth Rieder, Marvin J Grubman, Joseph L DeRisi, Teresa de Los Santos
The foot-and-mouth disease virus (FMDV) leader protease (L(pro)) inhibits host translation and transcription affecting the expression of several factors involved in innate immunity. In this study, we have identified the host transcription factor ADNP (activity dependent neuroprotective protein) as an L(pro) interacting protein by mass spectrometry. We show that L(pro) can bind to ADNP in vitro and in cell culture. RNAi of ADNP negatively affected virus replication and higher levels of interferon (IFN) and IFN-stimulated gene expression were detected...
February 17, 2017: Virology
https://www.readbyqxmd.com/read/28218713/transgene-expression-and-host-cell-responses-to-replication-defective-single-cycle-and-replication-competent-adenovirus-vectors
#5
Catherine M Crosby, Michael A Barry
Most adenovirus (Ad) vectors are E1 gene deleted replication defective (RD-Ad) vectors that deliver one transgene to the cell and all expression is based on that one gene. In contrast, E1-intact replication-competent Ad (RC-Ad) vectors replicate their DNA and their transgenes up to 10,000-fold, amplifying transgene expression markedly higher than RD-Ad vectors. While RC-Ad are more potent, they run the real risk of causing adenovirus infections in vector recipients and those that administer them. To gain the benefits of transgene amplification, but avoid the risk of Ad infections, we developed "single cycle" Ad (SC-Ad) vectors...
February 18, 2017: Genes
https://www.readbyqxmd.com/read/28216632/resveratrol-treatment-reveals-a-novel-role-for-hmgb1-in-regulation-of-the-type-1-interferon-response-in-dengue-virus-infection
#6
Nurhafiza Zainal, Chih-Peng Chang, Yi-Lin Cheng, Yan-Wei Wu, Robert Anderson, Shu-Wen Wan, Chia-Ling Chen, Tzong-Shiann Ho, Sazaly AbuBakar, Yee-Shin Lin
Dengue is one of the most significant mosquito-borne virus diseases worldwide, particularly in tropical and subtropical regions. This study sought to examine the antiviral activity of resveratrol (RESV), a phytoalexin secreted naturally by plants, against dengue virus (DENV) infection. Our data showed that RESV inhibits the translocation of high mobility group box 1 (HMGB1), a DNA binding protein that normally resides in the nucleus, into the cytoplasm and extracellular milieu. HMGB1 migrates out of the nucleus during DENV infection...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28216575/promising-targets-for-cancer-immunotherapy-tlrs-rlrs-and-sting-mediated-innate-immune-pathways
#7
REVIEW
Kai Li, Shuai Qu, Xi Chen, Qiong Wu, Ming Shi
Malignant cancers employ diverse and intricate immune evasion strategies, which lead to inadequately effective responses of many clinical cancer therapies. However, emerging data suggest that activation of the tolerant innate immune system in cancer patients is able, at least partially, to counteract tumor-induced immunosuppression, which indicates triggering of the innate immune response as a novel immunotherapeutic strategy may result in improved therapeutic outcomes for cancer patients. The promising innate immune targets include Toll-like Receptors (TLRs), RIG-I-like Receptors (RLRs), and Stimulator of Interferon Genes (STING)...
February 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28215221/targeting-chromatin-remodeling-in-inflammation-and-fibrosis
#8
J Yang, B Tian, A R Brasier
Mucosal surfaces of the human body are lined by a contiguous epithelial cell surface that forms a barrier to aerosolized pathogens. Specialized pattern recognition receptors detect the presence of viral pathogens and initiate protective host responses by triggering activation of the nuclear factor κB (NFκB)/RelA transcription factor and formation of a complex with the positive transcription elongation factor (P-TEFb)/cyclin-dependent kinase (CDK)9 and Bromodomain-containing protein 4 (BRD4) epigenetic reader...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28214886/adenovirus-vector-harboring-the-hbcag-and-tripeptidyl-peptidase-ii-genes-induces-potent-cellular-immune-responses-in-vivo
#9
Quanhui Tan, Siyuan Ma, Jianjun Hu, Xiaohua Chen, Yongsheng Yu, Zhenghao Tang, Guoqin Zang
BACKGROUND: Chronic hepatitis B virus (HBV) infection is associated with a weak but specific cellular immune response of the host to HBV. Tripeptidyl peptidaseⅡ (TPPⅡ), an intracellular macromolecule and proteolytic enzyme, plays an important complementary and compensatory role for the proteasome during viral protein degradation and major histocompatibility complex class I antigen presentation by inducing a specific cellular immune response in vivo. Based on a previous study, we aimed to explore the role of MHC class I antigen presentation in vivo and the mechanisms that may be involved...
January 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28213522/type-i-interferon-regulated-gene-expression-and-signaling-in-murine-mixed-glial-cells-lacking-signal-transducers-and-activators-of-transcription-1-or-2-or-interferon-regulatory-factor-9
#10
Wen Li, Markus J Hofer, Pattama Songkhunawej, So Ri Jung, Dale Hancock, Gareth Denyer, Iain L Campbell
Type I interferons (IFN-I) are critical in antimicrobial and antitumor defense. Although IFN-I signal via the interferon-stimulated gene factor 3 (ISGF3) complex consisting of STAT1, STAT2 and IRF9, IFN-I can mediate significant biological effects via ISGF3-independent pathways. For example, absence of STAT1, STAT2 or IRF9 exacerbates neurological disease in transgenic mice with CNS-production of IFN-Ι. Here we determined the role of IFN-I-driven, ISGF3-independent signaling in regulating global gene expression in STAT1, STAT2 or IRF9-deficient murine mixed glial cell cultures (MGCs)...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28210844/elevated-interferon-induced-protein-with-tetratricopeptide-repeats-3-ifit3-is-a-poor-prognostic-marker-in-pancreatic-ductal-adenocarcinoma
#11
Yue Zhao, Annelore Altendorf-Hofmann, Ioannis Pozios, Peter Camaj, Therese Däberitz, Xiaoyan Wang, Hanno Niess, Hendrik Seeliger, Felix Popp, Christopher Betzler, Utz Settmacher, Karl-Walter Jauch, Christiane Bruns, Thomas Knösel
PURPOSE: Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) gene from IFITs family is one gene among hundreds of IFN-stimulated genes. The potential role of IFIT3 in cancer is scarcely understood. In addition, the clinical relevance of IFIT3 is not yet known in pancreatic ductal adenocarcinoma (PDAC). We evaluated the prognostic significance of this gene in PDAC patients. METHODS: The expression of IFIT3 was analyzed in pancreatic cancer cell lines with different metastatic potential (FG and L3...
February 17, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28210256/transcriptomic-analysis-of-the-innate-antiviral-immune-response-in-porcine-intestinal-epithelial-cells-influence-of-immunobiotic-lactobacilli
#12
Leonardo Albarracin, Hisakazu Kobayashi, Hikaru Iida, Nana Sato, Tomonori Nochi, Hisashi Aso, Susana Salva, Susana Alvarez, Haruki Kitazawa, Julio Villena
Lactobacillus rhamnosus CRL1505 and Lactobacillus plantarum CRL1506 are immunobiotic strains able to increase protection against viral intestinal infections as demonstrated in animal models and humans. To gain insight into the host-immunobiotic interaction, the transcriptomic response of porcine intestinal epithelial (PIE) cells to the challenge with viral molecular associated pattern poly(I:C) and the changes in the transcriptomic profile induced by the immunobiotics strains CRL1505 and CRL1506 were investigated in this work...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28204879/interferon-stimulated-gene-15-expression-in-systemic-lupus-erythematosus-diagnostic-value-and-association-with-lymphocytopenia
#13
Y Yuan, H Ma, Z Ye, W Jing, Z Jiang
BACKGROUND: The aim of this study was to (a) assess the relationship between interferon-stimulated gene 15 (ISG15) expression and clinical manifestations of systemic lupus erythematosus (SLE) and (b) investigate the diagnostic value of ISG15 in SLE. PATIENTS AND METHODS: The study comprised 28 patients newly diagnosed with SLE, 10 patients with undifferentiated connective tissue disease, and 22 healthy volunteers. Of the SLE patients, 14 were chosen randomly to be followed up for 4 weeks...
February 15, 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/28202760/restriction-of-hcmv-replication-by-isg15-a-host-effector-regulated-by-cgas-sting-dsdna-sensing
#14
Christopher Bianco, Ian Mohr
Accumulation of the interferon-stimulated gene (ISG) 15 protein product, which is reversibly conjugated to numerous polypeptide targets, impacts the proteome and physiology of uninfected and infected cells. While many viruses, including human cytomegalovirus (HCMV) blunt host antiviral defenses by limiting ISG expression, the overall abundance of ISG15 monomer and protein conjugates rises in HCMV-infected cells. However, the molecular signals underlying ISG15 accumulation and whether the ISG15 polypeptide itself influences HCMV infection biology remain unknown...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202457/gain-of-function-samd9l-mutations-cause-a-syndrome-of-cytopenia-immunodeficiency-mds-and-neurological-symptoms
#15
Bianca Tesi, Josef Davidsson, Matthias Voss, Elisa Rahikkala, Tim D Holmes, Samuel C C Chiang, Jonna Komulainen-Ebrahim, Sorina Gorcenco, Alexandra Rundberg Nilsson, Tim Ripperger, Hannaleena Kokkonen, David Bryder, Thoas Fioretos, Jan-Inge Henter, Merja Möttönen, Riitta Niinimäki, Lars Nilsson, Cornelis Jan Pronk, Andreas Puschmann, Hong Qian, Johanna Uusimaa, Jukka Moilanen, Ulf Tedgård, Jörg Cammenga, Yenan T Bryceson
Several monogenic causes of familial myelodysplastic syndrome (MDS) have recently been identified. We studied two families with cytopenia, predisposition to MDS with chromosome 7 aberrations, immunodeficiency, and progressive cerebellar dysfunction. Genetic studies uncovered heterozygous missense mutations in SAMD9L, a tumor suppressor gene located on chromosome arm 7q. Consistent with a gain-of-function effect, ectopic expression of the two identified SAMD9L mutants decreased cell proliferation relative to wild-type protein...
February 15, 2017: Blood
https://www.readbyqxmd.com/read/28197148/avian-interferons-and-their-antiviral-effectors
#16
REVIEW
Diwakar Santhakumar, Dennis Rubbenstroth, Luis Martinez-Sobrido, Muhammad Munir
Interferon (IFN) responses, mediated by a myriad of IFN-stimulated genes (ISGs), are the most profound innate immune responses against viruses. Cumulatively, these IFN effectors establish a multilayered antiviral state to safeguard the host against invading viral pathogens. Considerable genetic and functional characterizations of mammalian IFNs and their effectors have been made, and our understanding on the avian IFNs has started to expand. Similar to mammalian counterparts, three types of IFNs have been genetically characterized in most avian species with available annotated genomes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28196762/enteric-helminth-induced-type-i-interferon-signalling-protects-against-pulmonary-virus-infection-through-interaction-with-the-microbiota
#17
Amanda J McFarlane, Henry J McSorley, Donald J Davidson, Paul M Fitch, Claire Errington, Karen J Mackenzie, Eva S Gollwitzer, Chris J C Johnston, Andrew S MacDonald, Michael R Edwards, Nicola L Harris, Benjamin J Marsland, Rick M Maizels, Jürgen Schwarze
BACKGROUND: Helminth parasites have been reported to have beneficial immune modulatory effects in allergic and autoimmune conditions and detrimental consequences in tuberculosis and some viral infections. Their role in co-infection with respiratory viruses is not clear. OBJECTIVE: Here, we investigated the effects of strictly enteric helminth infection with Heligmosomoides polygyrus on respiratory syncytial virus (RSV) infection in a mouse model. METHODS: A murine helminth/ RSV co-infection model was developed...
February 11, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28195391/rig-i-is-a-key-antiviral-interferon-stimulated-gene-against-hepatitis-e-virus-dispensable-of-interferon-production
#18
Lei Xu, Wenshi Wang, Yunlong Li, Xinying Zhou, Yuebang Yin, Yijin Wang, Robert A de Man, Luc J W van der Laan, Fen Huang, Nassim Kamar, Maikel P Peppelenbosch, Qiuwei Pan
: Interferons (IFNs) are broad antiviral cytokines that exert their function by inducing the transcription of hundreds of interferon-stimulated genes (ISGs). However, little is known about the antiviral potential of these cellular effectors on hepatitis E virus (HEV) infection, the leading cause of acute hepatitis globally. In this study, we profiled the antiviral potential of a panel of important human ISGs on HEV replication in cell culture models by overexpression of individual ISG...
February 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28194021/type-i-ifn-augments-il-27-dependent-trim25-expression-to-inhibit-hbv-replication
#19
Guangyun Tan, Qingfei Xiao, Hongxiao Song, Feng Ma, Fengchao Xu, Di Peng, Na Li, Xiaosong Wang, Junqi Niu, Pujun Gao, F Xiao-Feng Qin, Genhong Cheng
Hepatitis B virus (HBV) can cause chronic hepatitis B, which may lead to cirrhosis and liver cancer. Type I interferon (IFN) is an approved drug for the treatment of chronic hepatitis B. However, the fundamental mechanisms of antiviral action by type I IFN and the downstream signaling pathway are unclear. TRIM25 is an IFN-stimulated gene (ISG) that has an important role in RIG-I ubiquitination and activation. Whether TRIM25 is induced in liver cells by type I IFN to mediate anti-HBV function remains unclear...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28188292/cytosolic-dna-promotes-signal-transducer-and-activator-of-transcription-3-stat3-phosphorylation-by-tank-binding-kinase-1-tbk1-to-restrain-stat3-activity
#20
Hung-Ching Hsia, Jessica E Hutti, Albert S Baldwin
Cytosolic DNA can elicit beneficial as well as undesirable immune responses. For example, viral or microbial DNA triggers cell-intrinsic immune responses to defend against infections, whereas aberrant cytosolic accumulation of self-DNA results in pathological conditions, such as autoimmunity. Given the importance of these DNA-provoked responses, a better understanding of their molecular mechanisms is needed. Cytosolic DNA engages stimulator of interferon genes (STING) to activate TANK-binding kinase 1 (TBK1), which subsequently phosphorylates the transcription factor interferon regulatory factor 3 (IRF3) to promote interferon expression...
February 10, 2017: Journal of Biological Chemistry
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