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https://www.readbyqxmd.com/read/28818566/a-synthetic-human-cytomegalovirus-pp65-ie1-fusion-antigen-efficiently-induces-and-expands-virus-specific-t-cells
#1
Ellen K Link, Christine Brandmüller, Yasemin Suezer, Stefanie Ameres, Asisa Volz, Andreas Moosmann, Gerd Sutter, Michael H Lehmann
Infection with human cytomegalovirus (HCMV) can cause severe complications in newborns and immunocompromised patients, and a prophylactic or therapeutic vaccine against HCMV is not available. Here, we generated a HCMV vaccine candidate fulfilling the regulatory requirements for GMP-compliant production and clinical testing. A novel synthetic fusion gene consisting of the coding sequences of HCMV pp65 and IE1 having a deleted nuclear localization sequence and STAT2 binding domain was introduced into the genome of the attenuated vaccinia virus strain MVA...
August 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28808111/interferon-tau-promotes-cell-survival-and-inhibits-specific-luteolytic-genes-in-bovine-corpus-luteum
#2
Raghavendra Basavaraja, Emilia Przygrodzka, Bartosz Pawlinski, Zdzislaw Gajewski, Monika Marzena Kaczmarek, Rina Meidan
Interferon-tau (IFNT), a maternal recognition of pregnancy signals in domestic ruminants, suppress the release of luteolytic pulses of uterine prostaglandin F2a (PGF2a), thus extending the corpus luteum (CL) life span. We hypothesized that IFNT also exerts anti-luteolytic actions in bovine CL. To examine the direct effects of IFNT on bovine CL, luteal slices and enriched luteal endothelial cells (LECs) were utilized. We found that recombinant ovine IFNT (roIFNT) markedly elevates interferon-associated genes (STAT1, STAT2, and IRF9) and interferon-stimulated genes (ISGs: MX2, ISG15, & OAS1Y) in both models...
August 14, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28765967/influenza-virus-non%C3%A2-structural-protein-1-inhibits-the-production-of-interferon-%C3%AE-of-alveolar-epithelial-cells-upon-the-infection-of-influenza-a-h1n1
#3
Hao Jiang, Si-Mei Shen, Jie Yin, Peng-Peng Zhang, Yi Shi
Influenza A affects a large population worldwide. Influenza virus evades immune responses via various mechanisms, including through the modification of the immune microenvironment. Influenza virus non‑structural protein 1 (NS1) encoded by the virus genome inhibits type I interferon (IFN) signaling pathways, which is essential for viral clearance. However, the precise mechanisms of NS1‑mediated immune suppression remain poorly understood. The results of the present study demonstrated that mice infected with NS1‑expressing influenza A H1N1 virus had lower expression levels of IFNβ in the lung...
August 2, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28747540/historical-aspects-chronicling-the-discovery-of-ifnt
#4
Fuller Warren Bazer, William W Thatcher
It has been 42 years since a protein, now known as interferon tau (IFNT), was discovered in ovine conceptus-conditioned culture medium. In 1975, purification and testing of native IFNT revealed its unique antiluteolyic activity to prevent regression of corpora lutea on ovaries of nonpregnant ewes. Antiviral, antiproliferative and immunomodulatory properties of native and recombinant IFNT were also demonstrated. In addition, progesterone and IFNT were found to act cooperatively to silence expression of classical interferon stimulated genes in a cell-specific manner in ovine uterine luminal and superficial glandular epithelia...
July 26, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28714361/rna-editing-is-induced-by-type-i-interferon-in-esophageal-squamous-cell-carcinoma
#5
Jinyao Zhang, Zhaoli Chen, Zefang Tang, Jianbing Huang, Xueda Hu, Jie He
In recent years, abnormal RNA editing has been shown to play an important role in the development of esophageal squamous cell carcinoma, as such abnormal editing is catalyzed by ADAR (adenosine deaminases acting on RNA). However, the regulatory mechanism of ADAR1 in esophageal squamous cell carcinomas remains largely unknown. In this study, we investigated ADAR1 expression and its association with RNA editing in esophageal squamous cell carcinomas. RNA sequencing applied to esophageal squamous cell carcinoma clinical samples showed that ADAR1 expression was correlated with the expression of STAT1, STAT2, and IRF9...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28711499/inhibition-of-il-6-stat3-signaling-in-human-cancer-cells-using-evista
#6
Wei Shi, Dan Yan, Chongqiang Zhao, Miaomiao Xiao, Yina Wang, Haiyan Ma, Tianshu Liu, Hua Qin, Cuntai Zhang, Chenglong Li, Jiayuh Lin, Sheng Li, Jiagao Lv, Li Lin
Persistent activation of IL-6/STAT3 signaling pathway has been frequently detected in human cancer including breast cancer, colon cancer and multiple myeloma. IL-6/STAT3 can be a promising target for cancer prevent and treatment. However, few STAT3 inhibitors with high efficiency, specificity and safety is available for present clinical cancer therapy. Evista (Raloxifene·HCl) is known as selective estrogen receptor modulator which has been used for the prevention and treatment of osteoporosis and was approved for reducing the risk of invasive breast cancer...
July 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28707474/native-hydrophobic-binding-interactions-at-the-transition-state-for-association-between-the-taz1-domain-of-cbp-and-the-disordered-tad-stat2-are-not-a-requirement
#7
Ida Lindström, Jakob Dogan
A significant fraction of the eukaryotic proteome consists of proteins that are either partially or completely disordered under native-like conditions. Intrinsically disordered proteins (IDPs) are common in protein-protein interactions and are involved in numerous cellular processes. Although many proteins have been identified as disordered, much less is known about the binding mechanisms of the coupled binding and folding reactions involving IDPs. Here we have analyzed the rate-limiting transition state for binding between the TAZ1 domain of CREB binding protein and the intrinsically disordered transactivation domain of STAT2 (TAD-STAT2) by site-directed mutagenesis and kinetic experiments (Φ-value analysis) and found that the native protein-protein binding interface is not formed at the transition state for binding...
August 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28684637/interferon-stimulated-genes-are-transcriptionally-repressed-by-pr-in-breast-cancer
#8
Katherine Walter, Merit L Goodman, Hari Singhal, Jade Hall, Tianbao Li, Sean Holloran, Gloria Trinca, Katelin Gibson, Victor X Jin, Geoffrey Greene, Christy Hagan
The progesterone receptor (PR) regulates transcriptional programs that drive proliferation, survival, and stem cell phenotypes. Although the role of native progesterone in the development of breast cancer remains controversial, PR clearly alters the transcriptome in breast tumors. This study identifies a class of genes, interferon-stimulated genes (ISGs), potently downregulated by ligand-activated PR which have not been previously shown to be regulated by PR. Progestin-dependent transcriptional repression of ISGs was observed in breast cancer cell line models and human breast tumors...
July 6, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28680969/differential-antagonism-of-human-innate-immune-responses-by-tick-borne-phlebovirus-nonstructural-proteins
#9
Veronica V Rezelj, Ping Li, Vidyanath Chaudhary, Richard M Elliott, Dong-Yan Jin, Benjamin Brennan
In recent years, several newly discovered tick-borne viruses causing a wide spectrum of diseases in humans have been ascribed to the Phlebovirus genus of the Bunyaviridae family. The nonstructural protein (NSs) of bunyaviruses is the main virulence factor and interferon (IFN) antagonist. We studied the molecular mechanisms of IFN antagonism employed by the NSs proteins of human apathogenic Uukuniemi virus (UUKV) and those of Heartland virus (HRTV) and severe fever with thrombocytopenia syndrome virus (SFTSV), both of which cause severe disease...
May 2017: MSphere
https://www.readbyqxmd.com/read/28658622/lanosterol-modulates-tlr4-mediated-innate-immune-responses-in-macrophages
#10
Elisa Araldi, Marta Fernández-Fuertes, Alberto Canfrán-Duque, Wenwen Tang, Gary W Cline, Julio Madrigal-Matute, Jordan S Pober, Miguel A Lasunción, Dianqing Wu, Carlos Fernández-Hernando, Yajaira Suárez
Macrophages perform critical functions in both innate immunity and cholesterol metabolism. Here, we report that activation of Toll-like receptor 4 (TLR4) in macrophages causes lanosterol, the first sterol intermediate in the cholesterol biosynthetic pathway, to accumulate. This effect is due to type I interferon (IFN)-dependent histone deacetylase 1 (HDAC1) transcriptional repression of lanosterol-14α-demethylase, the gene product of Cyp51A1. Lanosterol accumulation in macrophages, because of either treatment with ketoconazole or induced conditional disruption of Cyp51A1 in mouse macrophages in vitro, decreases IFNβ-mediated signal transducer and activator of transcription (STAT)1-STAT2 activation and IFNβ-stimulated gene expression...
June 27, 2017: Cell Reports
https://www.readbyqxmd.com/read/28642132/unphosphorylated-stat3-regulates-the-antiproliferative-antiviral-and-gene-inducing-actions-of-type-i-interferons
#11
Susan R Pfeffer, Meiyun Fan, Ziyun Du, Chuan He Yang, Lawrence M Pfeffer
Type I interferon (IFNα/β) induces antiviral and antiproliferative responses in cells through the induction of IFN-stimulated genes (ISGs). Although the roles of IFN-activated STAT1 and STAT2 in the IFN response are well described, the function of STAT3 is poorly characterized. We investigated the role of STAT3 in the biological response to IFNα/β in mouse embryonic fibroblasts (MEFs) with a germ line deletion of STAT3. These STAT3 knockout (STAT3-KO) MEFs were reconstituted with STAT3 or the F705-STAT3 mutant (unphosphorylated STAT3) where the canonical Y705 tyrosine phosphorylation site was mutated...
August 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28559991/exogenous-mscs-ameliorate-hypoxia-reoxygenation-injury-in-renal-tubular-epithelial-cells-through-jak-stat-signaling-pathway-mediated-regulation-of-hmgb1
#12
Lei Zhang, Yan Wang, Junjie Ma, Xingqiang Lai, Jiali Fang, Guanghui Li, Lu Xu, Guanghui Pan, Zheng Chen
This study was conducted to investigate the repair mechanism of hypoxia/reoxygenation injury (HRI) in renal tubular epithelial cells (HK-2) by exogenous mesenchymal stem cells (MSCs). The activation of the JAK/STAT pathway in HK-2 cells after HRI and treatment of MSCs, JAK inhibitor WP1066 and STAT inhibitor SOCS3 was investigated using Western blot analysis. HK-2 cells were transfected with siRNA STAT3 and analyzed for expression of STAT3, JAK2 and HMGB1 using fluorescence quantitative PCR and Western blot...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28536310/the-prognostic-values-of-signal-transducers-activators-of-transcription-family-in-ovarian-cancer
#13
Saisai Li, Bo Sheng, Menghuang Zhao, Qi Shen, Haiyan Zhu, Xueqiong Zhu
Signal transducers activators of transcription (STATs), a family of latent cytoplasmic transcription factors, are composed of seven identified members (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6). STATs are associated with several biological processes such as cell proliferation, invasion and metastasis in various cancer types. In addition, STATs family have been well studied as a prognostic predictor for a considerable number of solid tumors. However, the prognostic value of STATs family in ovarian cancer patients remains unclear...
May 23, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28500614/irf9-stat2-fusion-protein-as-an-innate-immune-inducer-to-activate-mx-and-interferon-stimulated-gene-expression-in-zebrafish-larvae
#14
Chang-Jen Huang, Chih-Ming Chou, Huang-Wei Lien, Cheng-Ying Chu, Jhih-Yun Ho, Yimin Wu, Chia-Hsiung Cheng
Virus infection often causes large amounts of mortality during teleost larvae stage. Strong induction of innate immunity to increase survival rates of teleost larvae has been less reported. In this study, we present a zebrafish IRF9-Stat2 fusion protein (zIRF9-S2C) as a strong innate immunity inducer and characterized induction of interferon-stimulated genes (ISGs) in zebrafish larvae. zIRF9-S2C could mimic IFN-stimulated gene factor 3 (ISGF3) complex to constitutively activate transcription of Mx promoter through IFN-stimulatory element (ISRE) sites...
May 12, 2017: Marine Biotechnology
https://www.readbyqxmd.com/read/28499943/molecular-cloning-transcriptional-profiling-and-subcellular-localization-of-signal-transducer-and-activator-of-transcription-2-stat2-ortholog-from-rock-bream-oplegnathus-fasciatus
#15
S D N K Bathige, Navaneethaiyer Umasuthan, Thanthrige Thiunuwan Priyathilaka, William Shanthakumar Thulasitha, J D H E Jayasinghe, Qiang Wan, Bo-Hye Nam, Jehee Lee
Signal transducer and activator of transcription 2 (STAT2) is a key element that transduces signals from the cell membrane to the nucleus via the type I interferon-signaling pathway. Although the structural and functional aspects of STAT proteins are well studied in mammals, information on teleostean STATs is very limited. In this study, a STAT paralog, which is highly homologous to the STAT2 members, was identified from a commercially important fish species called rock bream and designated as RbSTAT2. The RbSTAT2 gene was characterized at complementary DNA (cDNA) and genomic sequence levels, and was found to possess structural features common with its mammalian counterparts...
August 30, 2017: Gene
https://www.readbyqxmd.com/read/28494868/interferon-receptor-signaling-pathways-regulating-pd-l1-and-pd-l2-expression
#16
Angel Garcia-Diaz, Daniel Sanghoon Shin, Blanca Homet Moreno, Justin Saco, Helena Escuin-Ordinas, Gabriel Abril Rodriguez, Jesse M Zaretsky, Lu Sun, Willy Hugo, Xiaoyan Wang, Giulia Parisi, Cristina Puig Saus, Davis Y Torrejon, Thomas G Graeber, Begonya Comin-Anduix, Siwen Hu-Lieskovan, Robert Damoiseaux, Roger S Lo, Antoni Ribas
PD-L1 and PD-L2 are ligands for the PD-1 immune inhibiting checkpoint that can be induced in tumors by interferon exposure, leading to immune evasion. This process is important for immunotherapy based on PD-1 blockade. We examined the specific molecules involved in interferon-induced signaling that regulates PD-L1 and PD-L2 expression in melanoma cells. These studies revealed that the interferon-gamma-JAK1/JAK2-STAT1/STAT2/STAT3-IRF1 axis primarily regulates PD-L1 expression, with IRF1 binding to its promoter...
May 9, 2017: Cell Reports
https://www.readbyqxmd.com/read/28472186/stat2-is-involved-in-the-pathogenesis-of-psoriasis-by-promoting-cxcl11-and-ccl5-production-by-keratinocytes
#17
Claus Johansen, Anne Hald Rittig, Maike Mose, Trine Bertelsen, Isabella Weimar, Jakob Nielsen, Thomas Andersen, Tue Kruse Rasmussen, Bent Deleuran, Lars Iversen
The JAK/STAT signaling pathway is suggested to play an important role in the pathogenesis of psoriasis, and recently JAK/STAT inhibitors have shown promising results in psoriasis treatment. The present study aimed to characterize the role of STAT2 in psoriasis. We demonstrated an increased expression of STAT2 and an increased level of phosphorylated/activated STAT2 in lesional compared with nonlesional psoriatic skin. Gene silencing of STAT2 by siRNA in human keratinocytes revealed that upon IFNα stimulation CXCL11 and CCL5 were the only two cytokines, among 102 analyzed, found to be regulated through a STAT2-dependent mechanism...
2017: PloS One
https://www.readbyqxmd.com/read/28468880/selective-activation-of-type-ii-interferon-signaling-by-zika-virus-ns5-protein
#18
Vidyanath Chaudhary, Kit-San Yuen, Jasper Fuk-Woo Chan, Ching-Ping Chan, Pei-Hui Wang, Jian-Piao Cai, Shuo Zhang, Mifang Liang, Kin-Hang Kok, Chi-Ping Chan, Kwok-Yung Yuen, Dong-Yan Jin
Severe complications of Zika virus (ZIKV) infection might be caused by inflammation, but how ZIKV induces proinflammatory cytokines is not understood. In this study, we show opposite regulatory effects of the ZIKV NS5 protein on interferon (IFN) signaling. Whereas ZIKV and its NS5 protein were potent suppressors of type I and type III IFN signaling, they were found to activate type II IFN signaling. Inversely, IFN-γ augmented ZIKV replication. NS5 interacted with STAT2 and targeted it for ubiquitination and degradation, but it had no influence on STAT1 stability or nuclear translocation...
July 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28442624/unphosphorylated-isgf3-drives-constitutive-expression-of-interferon-stimulated-genes-to-protect-against-viral-infections
#19
Wenshi Wang, Yuebang Yin, Lei Xu, Junhong Su, Fen Huang, Yijin Wang, Patrick P C Boor, Kan Chen, Wenhui Wang, Wanlu Cao, Xinying Zhou, Pengyu Liu, Luc J W van der Laan, Jaap Kwekkeboom, Maikel P Peppelenbosch, Qiuwei Pan
Interferon (IFN)-stimulated genes (ISGs) are antiviral effectors that are induced by IFNs through the formation of a tripartite transcription factor ISGF3, which is composed of IRF9 and phosphorylated forms of STAT1 and STAT2. However, we found that IFN-independent ISG expression was detectable in immortalized cell lines, primary intestinal and liver organoids, and liver tissues. The constitutive expression of ISGs was mediated by the unphosphorylated ISGF3 (U-ISGF3) complex, consisting of IRF9 together with unphosphorylated STAT1 and STAT2...
April 25, 2017: Science Signaling
https://www.readbyqxmd.com/read/28441586/kobuvirus-vp3-protein-restricts-the-ifn-%C3%AE-triggered-signaling-pathway-by-inhibiting-stat2-irf9-and-stat2-stat2-complex-formation
#20
Qianqian Peng, Xi Lan, Chen Wang, Yujie Ren, Ningning Yue, Junyong Wang, Bo Zhong, Qiyun Zhu
Emerged porcine kobuvirus (PKV) has adversely affected the global swine industry since 2008, but the etiological biology of PKV is unclear. Screening PKV-encoded structural and non-structural proteins with a type I IFN-responsive luciferase reporter showed that PKV VP3 protein inhibited the IFN-β-triggered signaling pathway, resulting in the decrease of VSV-GFP replication. QPCR data showed that IFN-β downstream cytokine genes were suppressed without cell-type specificity as well. The results from biochemical experiments indicated that PKV VP3 associated with STAT2 and IRF9, and interfered with the formation of the STAT2-IRF9 and STAT2-STAT2 complex, impairing nuclear translocation of STAT2 and IRF9...
July 2017: Virology
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