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Stimulator of interferon genes

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https://www.readbyqxmd.com/read/29777205/oviduct-epithelium-induces-interferon-tau-in-bovine-day-4-embryos-which-generates-an-anti-inflammatory-response-in-immune-cells
#1
Anup K Talukder, Mohammad B Rashid, Mohamed S Yousef, Kazuya Kusama, Takashi Shimizu, Masayuki Shimada, Susan S Suarez, Kazuhiko Imakawa, Akio Miyamoto
Recent studies indicate that communication between the bovine embryo and the mother begins in the oviduct. Here, we aimed to investigate the effect of embryos on bovine oviducts for their immune responses using an in vitro model. First, zygotes were cultured with or without bovine oviduct epithelial cells (BOECs) for 4 days, when embryos had reached the 16-cell stage. At that time, we detected interferon-tau (IFNT) in embryos co-cultured with BOECs, but not in embryos cultured alone. Next, peripheral blood mononuclear cells (PBMCs) were incubated either in media from embryo alone cultures or from co-cultures of embryos with BOECs...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29774240/mannan-induced-nos2-in-macrophages-enhances-il-17-driven-psoriatic-arthritis-by-innate-lymphocytes
#2
Jianghong Zhong, Tatjana Scholz, Anthony C Y Yau, Simon Guerard, Ulrike Hüffmeier, Harald Burkhardt, Rikard Holmdahl
Previous identification of the inducible nitric oxide synthase (NOS2) gene as a risk allele for psoriasis (Ps) and psoriatic arthritis (PsA) suggests a possible pathogenic role of nitric oxide (NO). Using a mouse model of mannan-induced Ps and PsA (MIP), where macrophages play a regulatory role by releasing reactive oxygen species (ROS), we found that NO was detectable before disease onset in mice, independent of a functional nicotinamide adenine dinucleotide phosphate oxidase 2 complex. MIP was suppressed by either deletion of Nos2 or inhibition of NO synthases with NG-nitro-l-arginine methyl ester, demonstrating that Nos2-derived NO is pathogenic...
May 2018: Science Advances
https://www.readbyqxmd.com/read/29772254/effect-of-interferon-alpha-and-cyclosporine-treatment-separately-and-in-combination-on-middle-east-respiratory-syndrome-coronavirus-mers-cov-replication-in-a-human-in-vitro-and-ex-vivo-culture-model
#3
H S Li, Denise I T Kuok, M C Cheung, Mandy M T Ng, K C Ng, Kenrie P Y Hui, J S Malik Peiris, Michael C W Chan, John M Nicholls
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has emerged as a coronavirus infection of humans in the past 5 years. Though confined to certain geographical regions of the world, infection has been associated with a case fatality rate of 35%, and this mortality may be higher in ventilated patients. As there are few readily available animal models that accurately mimic human disease, it has been a challenge to ethically determine what optimum treatment strategies can be used for this disease. We used in-vitro and human ex-vivo explant cultures to investigate the effect of two immunomodulatory agents, interferon alpha and cyclosporine, singly and in combination, on MERS-CoV replication...
May 14, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29769653/isg15-in-antiviral-immunity-and-beyond
#4
REVIEW
Yi-Chieh Perng, Deborah J Lenschow
The host response to viral infection includes the induction of type I interferons and the subsequent upregulation of hundreds of interferon-stimulated genes. Ubiquitin-like protein ISG15 is an interferon-induced protein that has been implicated as a central player in the host antiviral response. Over the past 15 years, efforts to understand how ISG15 protects the host during infection have revealed that its actions are diverse and pathogen-dependent. In this Review, we describe new insights into how ISG15 directly inhibits viral replication and discuss the recent finding that ISG15 modulates the host damage and repair response, immune response and other host signalling pathways...
May 16, 2018: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/29769349/hiv-1-activation-of-innate-immunity-depends-strongly-on-the-intracellular-level-of-trex1-and-sensing-of-incomplete-reverse-transcription-products
#5
Swati Kumar, James H Morrison, David Dingli, Eric Poeschla
TREX1 has been reported to degrade cytosolic immune-stimulatory DNA, including viral DNA generated during HIV-1 infection, but the dynamic range of its capacity to suppress innate immune stimulation is unknown and its full role in the viral life cycle remains unclear. A main purpose of our study was to determine how the intracellular level of TREX1 affects HIV-1 activation and avoidance of innate immunity. Using stable over-expression and CRISPR-mediated gene disruption, we engineered a range of TREX1 levels in human THP-1 monocytes...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29769339/differential-responses-by-human-respiratory-epithelial-cell-lines-to-respiratory-syncytial-virus-reflect-distinct-patterns-of-infection-control
#6
Philippa Hillyer, Rachel Shepard, Megan Uehling, Mina Krenz, Faruk Sheikh, Kalyn R Thayer, Lei Huang, Lihan Yan, Debasis Panda, Cindy Luongo, Ursula J Buchholz, Peter L Collins, Raymond P Donnelly, Ronald L Rabin
RSV infects small foci of respiratory epithelial cells via infected droplets. Infection induces expression of types I and III interferons (IFNs) and pro-inflammatory cytokines, the balance of which may restrict viral replication and affect disease severity. We explored this balance by infecting two respiratory epithelial cell lines with low doses of recombinant RSV expressing green fluorescent protein (rgRSV). A549 cells were highly permissive whereas BEAS-2B cells restricted infection to individual cells or small foci...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29762170/a-compartmentalized-type-i-interferon-response-in-the-gut-during-chronic-hiv-1-infection-is-associated-with-immunopathogenesis
#7
Stephanie M Dillon, Kejun Guo, Gregory L Austin, Sara Gianella, Phillip A Engen, Ece A Mutlu, John Losurdo, Garth Swanson, Prachi Chakradeo, Ali Keshavarzian, Alan L Landay, Mario Santiago, Cara Wilson
OBJECTIVE(S): Type I IFN (IFN-I) responses confer both protective and pathogenic effects in persistent virus infections. IFN-I diversity, stage of infection and tissue compartment may account for this dichotomy. The gut is a major site of early HIV-1 replication and microbial translocation, but the nature of the IFN-I response in this compartment remains unclear. DESIGN: Samples were obtained from two IRB-approved cross-sectional studies. The first study included individuals with chronic, untreated HIV-1 infection (n = 24) and age/gender balanced uninfected controls (n = 14)...
May 11, 2018: AIDS
https://www.readbyqxmd.com/read/29759327/immunotherapy-responsive-childhood-neurodegeneration-with-systemic-and-central-nervous-system-inflammation
#8
Mario Sa, Yael Hacohen, Lucy Alderson, W K Kling Chong, Glenn Anderson, Thomas S Jacques, David Neubauer, Elzbieta Szczepanik, Ming Lim, Marios Kaliakatsos
Subacute neuroregression in association with raised neopterin and overexpression of interferon stimulated genes (ISGs) could indicate a type 1 interferonopathy. Here we describe a novel immunotherapy-responsive, clinico-immunological and imaging phenotype with evidence of innate immune activation. Three children (patient 1: 22-month-old boy; patient 2: 5-year-old girl; patient 3: 4-year-old girl) presented with asymmetric bilateral mixed dystonia and spasticity, regression in language (expressive more than receptive) and bulbar symptoms with no evidence of seizures...
April 27, 2018: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/29758486/poly-i-c-and-lps-induce-distinct-immune-responses-by-ovarian-stromal-fibroblasts
#9
Mickey V Patel, Zheng Shen, Charles R Wira
Despite its anatomical location, the ovary is a site of pathogen exposure in the human female reproductive tract (FRT). However, the role of ovarian stromal fibroblasts in immune protection is unclear. We generated a population of ovarian stromal fibroblasts derived from normal human ovaries that expressed the pattern recognition receptors TLR3, TLR4, RIG-I, & MDA5. Poly (I:C) and LPS, respective mimics of viral and bacterial infections, selectively upregulated antiviral gene expression and secretion of chemokines and antimicrobials...
May 9, 2018: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/29753657/irf-1-rig-i-and-mda5-display-potent-antiviral-activities-against-norovirus-coordinately-induced-by-different-types-of-interferons
#10
Wen Dang, Lei Xu, Yuebang Yin, Sunrui Chen, Wenshi Wang, Mohamad S Hakim, Kyeong-Ok Chang, Maikel P Peppelenbosch, Qiuwei Pan
Norovirus represents the main cause of acute nonbacterial gastroenteritis worldwide. In immunocompromised patients, it bears high risk of causing chronic infection with significant morbidity and mortality. The lack of specific treatment prompts the development of anti-norovirus agents. In this study, we have investigated the role of interferon (IFN) response and evaluated antiviral activities of different IFNs against human norovirus (HuNoV) replication using a HuNoV replicon model. We found that HuNoV RNA replication was sensitive to all types of IFNs, including IFNα (type I), IFNγ (type II), IFNλ1 and 3 (type III)...
May 10, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29751735/identification-of-compounds-that-prolong-type-i-interferon-signaling-as-potential-vaccine-adjuvants
#11
Nikunj M Shukla, Kei-Ichiro Arimoto, Shiyin Yao, Jun-Bao Fan, Yue Zhang, Fumi Sato-Kaneko, Fitzgerald S Lao, Tadashi Hosoya, Karen Messer, Minya Pu, Howard B Cottam, Dennis A Carson, Tomoko Hayashi, Dong-Er Zhang, Maripat Corr
Vaccines are reliant on adjuvants to enhance the immune stimulus, and type I interferons (IFNs) have been shown to be beneficial in augmenting this response. We were interested in identifying compounds that would sustain activation of an endogenous type I IFN response as a co-adjuvant. We began with generation of a human monocytic THP-1 cell line with an IFN-stimulated response element (ISRE)-β-lactamase reporter construct for high-throughput screening. Pilot studies were performed to optimize the parameters and conditions for this cell-based Förster resonance energy transfer (FRET) reporter assay for sustaining an IFN-α-induced ISRE activation signal...
May 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29751576/thymoquinone-suppresses-irf-3-mediated-expression-of-type-i-interferons-via-suppression-of-tbk1
#12
Nur Aziz, Young-Jin Son, Jae Youl Cho
Interferon regulatory factor (IRF)-3 is known to have a critical role in viral and bacterial innate immune responses by regulating the production of type I interferon (IFN). Thymoquinone (TQ) is a compound derived from black cumin ( Nigella sativa L.) and is known to regulate immune responses by affecting transcription factors associated with inflammation, including nuclear factor-κB (NF-κB) and activator protein-1 (AP-1). However, the role of TQ in the IRF-3 signaling pathway has not been elucidated...
May 3, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29748576/autophagy-diminishes-the-early-interferon-%C3%AE-response-to-influenza-a-virus-resulting-in-differential-expression-of-interferon-stimulated-genes
#13
Brieuc P Perot, Jeremy Boussier, Nader Yatim, Jeremy S Rossman, Molly A Ingersoll, Matthew L Albert
Influenza A virus (IAV) infection perturbs metabolic pathways such as autophagy, a stress-induced catabolic pathway that crosstalks with cellular inflammatory responses. However, the impact of autophagy perturbation on IAV gene expression or host cell responses remains disputed. Discrepant results may be a reflection of in vivo studies using cell-specific autophagy-related (Atg) gene-deficient mouse strains, which do not delineate modification of developmental programmes from more proximal effects on inflammatory response...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29746888/nearly-neutral-evolution-in-ifnl3-gene-retains-the-immune-function-to-detect-and-clear-the-viral-infection-in-hcv
#14
Pratichi Singh, J Febin Prabhu Dass
IFNL3 gene plays a crucial role in immune defense against viruses. It induces the interferon stimulated genes (ISGs) with antiviral properties by activating the JAK-STAT pathway. In this study, we investigated the evolutionary force involved in shaping the IFNL3 gene to perform its downstream function as a regulatory gene in HCV clearance. We have selected 25 IFNL3 coding sequences with human gene as a reference sequence and constructed a phylogeny. Furthermore, rate of variation, substitution saturation test, phylogenetic informativeness and differential selection were also analysed...
May 7, 2018: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/29746837/an-immunocompetent-mouse-model-of-zika-virus-infection
#15
Matthew J Gorman, Elizabeth A Caine, Konstantin Zaitsev, Matthew C Begley, James Weger-Lucarelli, Melissa B Uccellini, Shashank Tripathi, Juliet Morrison, Boyd L Yount, Kenneth H Dinnon, Claudia Rückert, Michael C Young, Zhe Zhu, Shelly J Robertson, Kristin L McNally, Jing Ye, Bin Cao, Indira U Mysorekar, Gregory D Ebel, Ralph S Baric, Sonja M Best, Maxim N Artyomov, Adolfo Garcia-Sastre, Michael S Diamond
Progress toward understanding Zika virus (ZIKV) pathogenesis is hindered by lack of immunocompetent small animal models, in part because ZIKV fails to effectively antagonize Stat2-dependent interferon (IFN) responses in mice. To address this limitation, we first passaged an African ZIKV strain (ZIKV-Dak-41525) through Rag1-/- mice to obtain a mouse-adapted virus (ZIKV-Dak-MA) that was more virulent than ZIKV-Dak-41525 in mice treated with an anti-Ifnar1 antibody. A G18R substitution in NS4B was the genetic basis for the increased replication, and resulted in decreased IFN-β production, diminished IFN-stimulated gene expression, and the greater brain infection observed with ZIKV-Dak-MA...
May 9, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29746256/glucocorticoid-receptor-dimers-control-intestinal-stat1-and-tnf-induced-inflammation-in-mice
#16
Marlies Ballegeer, Kelly Van Looveren, Steven Timmermans, Melanie Eggermont, Sofie Vandevyver, Fabien Thery, Karen Dendoncker, Jolien Souffriau, Jolien Vandewalle, Lise Van Wyngene, Riet De Rycke, Nozomi Takahashi, Peter Vandenabeele, Jan Tuckermann, Holger M Reichardt, Francis Impens, Rudi Beyaert, Karolien De Bosscher, Roosmarijn E Vandenbroucke, Claude Libert
Tumor Necrosis Factor (TNF) is an important mediator in numerous inflammatory diseases, e.g., in inflammatory bowel diseases (IBD). In IBD, acute increases in TNF production can lead to disease flares. Glucocorticoids (GCs), which are steroids that bind and activate the glucocorticoid receptor (GR), are able to protect animals and humans against acute TNF-induced inflammatory symptoms. Mice with a poor transcriptional response of GR-dimer-dependent target genes were studied in a model of TNF-induced lethal inflammation...
May 10, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29745062/long-non-coding-rna-gas5-is-induced-by-interferons-and-plays-an-antitumor-role-in-esophageal-squamous-cell-carcinoma
#17
Jianbing Huang, Yuan Li, Zhiliang Lu, Yun Che, Shouguo Sun, Shuangshuang Mao, Yuanyuan Lei, Ruochuan Zang, Ning Li, Nan Sun, Jie He
The long non-coding RNA GAS5 has been reported as a tumor suppressor in many cancers. However, its functions and mechanisms remain largely unknown in esophageal squamous cell carcinoma (ESCC). In this study, we found that GAS5 was over-expressed in ESCC tissue compared with that in normal esophageal tissue in a public database. Functional studies showed that GAS5 could inhibit ESCC cell proliferation, migration and invasion in vitro. Further analysis revealed that GAS5 was regulated by interferon (IFN) responses via the JAK-STAT pathway...
May 9, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29743376/transmembrane-protein-pul50-of-human-cytomegalovirus-inhibits-isgylation-by-downregulating-ube1l
#18
Myoung Kyu Lee, Ye Ji Kim, Young-Eui Kim, Tae-Hee Han, Jens Milbradt, Manfred Marschall, Jin-Hyun Ahn
Interferon-stimulated gene (ISG) 15 encodes a ubiquitin-like protein that can be conjugated to proteins via an enzymatic cascade involving the E1, E2, and E3 enzymes. ISG15 expression and protein ISGylation modulate viral infection; however, the viral mechanisms regulating the function of ISG15 and ISGylation are not well understood. We recently showed that ISGylation suppresses the growth of human cytomegalovirus (HCMV) at multiple steps of the virus life cycle, and that the virus-encoded pUL26 protein inhibits protein ISGylation...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29743370/herpes-simplex-virus-1-inhibits-tank-binding-kinase-1-through-formation-of-the-us11-hsp90-complex
#19
Xing Liu, David Main, Yijie Ma, Bin He
The Us11 protein of herpes simplex virus 1 (HSV-1) is an accessory factor with multiple functions. In virus-infected cells, it inhibits double-stranded RNA dependent protein kinase PKR, 2',5'-oligoadenylate synthetase, RIG-I and MDA-5. However, its precise role is incompletely defined. By screening human cDNA library, we show that the Us11 protein targets heat shock protein 90 (Hsp90), which inactivates TANK binding kinase 1 (TBK1) and antiviral immunity. When ectopically expressed, HSV-1 Us11 precludes the access of TBK1 to Hsp90 and IFN promoter activation...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29743346/pgd2-dp2-receptor-activation-promotes-severe-viral-bronchiolitis-by-suppressing-ifn-%C3%AE-production
#20
Rhiannon B Werder, Jason P Lynch, Jennifer C Simpson, Vivian Zhang, Nick H Hodge, Matthew Poh, Elizabeth Forbes-Blom, Christina Kulis, Mark L Smythe, John W Upham, Kirsten Spann, Mark L Everard, Simon Phipps
Prostaglandin D2 (PGD2) signals through PGD2 receptor 2 (DP2, also known as CRTH2) on type 2 effector cells to promote asthma pathogenesis; however, little is known about its role during respiratory syncytial virus (RSV) bronchiolitis, a major risk factor for asthma development. We show that RSV infection up-regulated hematopoietic prostaglandin D synthase expression and increased PGD2 release by cultured human primary airway epithelial cells (AECs). Moreover, PGD2 production was elevated in nasopharyngeal samples from young infants hospitalized with RSV bronchiolitis compared to healthy controls...
May 9, 2018: Science Translational Medicine
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